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1. To investigate the contribution of sedation to the cardiovascular effects induced by clonidine, we studied patients with essential hypertension on two separate occasions when similar levels of sedation were induced by clonidine and nitrazepam. 2. After clonidine, there was a fall in blood pressure, heart rate, digital skin vascular resistance and plasma noradrenaline which is consistent with its ability to reduce sympathetic outflow. Dissociation of the circulatory/neurohormonal and sedative responses after clonidine indicated that sedation alone is not an important factor in the blood pressure lowering effect of clonidine. 3. The absence of a fall in blood pressure, heart rate, digital skin vascular resistance and plasma noradrenaline after nitrazepam further suggest that sedation did not influence the hypotensive response in essential hypertension. [ABSTRACT FROM AUTHOR]

The mechanisms of the cardiovascular and renin responses to vasoactive intestinal polypeptide (VIP) are unclear. Rabbit studies suggest that VIP-induced tachycardia is largely beta-adrenoceptor mediated, but that the renin response may be partially prostaglandin-dependent. To examine the relative importance of prostaglandins and reflex sympathetic activation in the haemodynamic and renin responses to VIP infusion in man, we completed two randomised single-blind crossover studies in two groups of six healthy male volunteers (aged 24-35 years). We recorded the effects of indomethacin and propranolol pretreatment on VIP-related changes in heart rate (HR), blood pressure (BP), forearm vascular resistance (FVR), plasma renin activity (PRA), plasma noradrenaline (PNA) and plasma arginine vasopressin (AVP) concentrations. Intravenous VIP (calculated dose: 6 pmol kg-1 min-1) produced cutaneous flushing, increased HR and PRA, decreased FVR, but did not alter mean arterial BP or AVP levels. Indomethacin (375 mg over 3 days) lowered basal PRA and propranolol (circa 40 mg i.v. over 60 min) decreased resting HR and increased FVR. Although indomethacin and propranolol reduced the absolute rise in PRA and HR, respectively, during VIP infusion, the percentage changes were no different from control. Neither drug altered the flush response to VIP and propranolol did not affect the fall in FVR. We conclude that the measured cardiovascular responses to VIP infusion in man are probably direct and do not involve a significant contribution from reflex sympathetic stimulation, nor prostaglandin release. [ABSTRACT FROM AUTHOR]

1. The effects of change from a high to low sodium diet upon renal sodium and water excretion and hormone responses were studied in patients with dissociated sympathetic control (DS, tetraplegic) and controls with sympathetic control largely intact (IS, paraplegic). 2. Total and fractional urinary sodium excretion fell in response to sodium restriction in both groups, but the fall in fractional sodium excretion was greater in the DS group compared with the IS group (DS, 1.34 +/- 0.12 to 0.42 +/- 0.05%; IS, 0.96 +/- 0.08 to 0.52 +/- 0.06%). 3. Supine mean arterial pressure fell during the low salt period in the DS group (80.2 +/- 2.7 to 74.4 +/- 2.3 mmHg) but was unaffected by salt restriction in the IS group (101 +/- 2.3 to 98.8 +/- 2.7 mmHg). In the DS group, creatinine clearance remained constant throughout the low salt period (103.7 +/- 7.9 to 98.3 +/- 9.7 ml min-1), but fell during salt restriction in the IS group (101.4 +/- 8.5 to 83.2 +/- 5 ml min-1). 4. Plasma renin activity was lower during salt loading in DS subjects but increased more rapidly and to higher levels in response to salt restriction (DS, 1021 +/- 142 to 4439 +/- 355; IS, 1765 +/- 269 to 3683 +/- 465 pg angiotensin I ml-1 h-1). Plasma atrial natriuretic peptide concentration was higher in the DS group during salt loading and salt restriction (DS, 37.6 +/- 5.6 to 22 +/- 3.8; IS, 20.2 +/- 2.3 to 11 +/- 1.6 pg ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

After the development of blood pressure measurements in humans, the association of high blood pressure with renal disease was established. Injection of extracts of various organs in an attempt to replace their secretions was common in the 19th century, and it was therefore natural for Tigerstedt and Bergman to investigate the effects of renal extracts. In this way, they discovered renin. This paper covers the methods by which its mode of action was uncovered, as well as its relation to renal ischemia and hypertension.

Background: Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated., Methods and Results: The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors., Conclusions: Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension.

Patients with ileostomies show an early diuresis when sodium restricted; this, together with an obligatory ileal sodium loss, predisposes them to severe salt and water depletion. The role of arginine vasopressin in this circumstance and whether it is natriuretic, or antinatriuretic, is unclear. There is also controversy over its likely effect on small bowel fluid reabsorption. We have examined the effect of the non-pressor (V2) synthetic vasopressin analogue 1-deamino-8-D-arginine (desmopressin) on renal and ileal sodium and water excretion in ileostomy patients during acute adaptation to a low sodium diet. Patients were studied on two separate occasions (nonrandomised) with and without the administration of desmopressin (0.75 micrograms intramuscular, three times a day). In eight subjects without desmopressin there was pronounced diuresis on the first low sodium day, associated with a fall in renal sodium excretion and no change in ileal output or composition. In five (of the original) subjects with desmopressin there was pronounced antidiuresis, no change in renal sodium excretion, and no change in ileal output or composition. In both studies rises in plasma renin activity and salivary aldosterone concentration lagged behind the early decline in renal sodium excretion. We have confirmed the phenomenon of 'low sodium' diuresis after sodium restriction in ileostomy patients and shown that it can be prevented by desmopressin. Desmopressin has no direct or indirect effect on renal sodium excretion or ileal fluid and electrolyte loss in humans.

Objective: To demonstrate the magnitude, timing, and cause of changes in blood pressure that occur in migrants from a low blood pressure population on moving to an urban area., Design: A controlled longitudinal observational study of migrants as soon after migration as possible and follow up at three, six, 12, 18, and 24 months after migration. A cohort of controls living in a rural area who were matched for age, sex, and locality were also observed at the same periods., Setting: 35 Villages on the northern shores of Lake Victoria in western Kenya and Nairobi., Participants: 325 Members of the Luo tribe aged 15 to 34 years who had migrated to Nairobi and 267 controls living in villages. The numbers of both groups reduced during follow up such that only 63 migrants and 143 controls were followed up for two years., Main Outcome Measures: A medical questionnaire and three 24 hour diet histories were completed by migrants and controls. Height, weight, pulse, and blood pressure were measured. Three 12 hour overnight urine samples were collected from all participants and analysed for sodium, potassium, and creatinine concentrations., Results: The mean systolic blood pressure of migrants was significantly higher than that of controls throughout the study, and the distribution of blood pressure was shifted to the right compared with controls. The mean diastolic blood pressure of the two groups diverged over time. Blood pressure differences were not due to selective migration. The migrants' mean urinary sodium:potassium ratio was higher than that of controls (p less than 0.001) throughout, and weight and pulse rate were also higher among migrants, although differences diminished with time., Conclusions: Urinary sodium:potassium ratio, pulse rate, and weight are important predictors of increased blood pressure among migrants from a low blood pressure community and may also be implicated in the initiation of essential hypertension.

Sixteen hypertensive patients received pindolol (10-45 mg/day); mean +/- SD, 28.75 +/- 15.22) for 3-8 weeks in a placebo-controlled, single-blind, crossover study. Supine and standing blood pressures (BP) were lowered, whereas effective renal plasma flow and glomerular filtration rates (estimated from the clearances of Hippuran and EDTA during oral water loading) did not change consistently. "Blood volume" (calculated from 125I-human serum albumin space and microhaematocrit) increased, with a corresponding reduction in serum albumin but without a change in body weight or "total body water" (T2O space). The results suggest a transfer of water from the interstitial to the intravascular compartment. This was supported by estimates of "extracellular fluid volume" (EDTA space) and "interstitial volume" (EDTA) minus human serum albumin spaces) in 3 subjects. The changes produced in "blood volume" correlated with those in BP. Plasma levels of noradrenaline, renin activity, and aldosterone were reduced, as was renal aldosterone excretion. There was no correlation between the changes produced by pindolol in BP and these hormone levels. Pindolol treatment reduced serum calcium concentration. There was a strong positive correlation between changes in BP and serum calcium and renal calcium excretion.

The mechanism of alteration in renal sodium excretion in response to dietary changes is complex and poorly understood. A gut 'sensor' might exist which regulates the renal response and this may involve one or more of the now ubiquitous gastrointestinal peptides. Several of these gut peptides, including neurotensin, have been found within the kidney. Plasma levels of neurotensin, which is both a circulating hormone and putative neurotransmitter, rise promptly on feeding. When infused into the conscious rabbit, neurotensin produces a dose-related fall in renal sodium excretion.

1 The effect of calcium on the inhibition of renin secretion by biologically active angiotensin was investigated in the isolated rat kidney perfused with Krebs-Ringer saline.2 In the presence of calcium (3.7 mM), asp(NH(2))'-angiotensin II suppressed both basal and isoprenaline-stimulated renin secretion. Renal perfusion pressure, which was increased by the infusion of angiotensin, returned to control levels when isoprenaline was added.3 When the calcium concentration was reduced to 0.32 mM, the vasoconstriction produced by angiotensin was abolished although the inhibitory effect on renin secretion was still evident.4 In the absence of calcium, angiotensin no longer suppressed basal renin secretion and a prompt increase in renin secretion occurred when isoprenaline was added.5 The higher basal renin levels which were observed in calcium-free perfusions, suggest the existence of an intrarenal calcium-dependent mechanism that regulates basal renin secretion.6 These observations indicate that the inhibitory effect of biologically active angiotensin, on basal and isoprenaline-stimulated renin secretion, is functionally related to the contractor response by its dependence on calcium. The recognition that the renin-producing cells are modified smooth muscle cells supports this association

Six healthy males received vasoactive intestinal polypeptide (VIP; 6 pmol kg-1 min-1) by intravenous infusion for 90 min, with 60 min control periods before and after. Plasma VIP levels rose by about 100 pmol l-1 during the infusion. VIP produced changes in heart rate and blood pressure consistent with generalized vasodilatation, but there were no significant changes in effective renal plasma flow or glomerular filtration rate. Both plasma solids and haematocrit rose by about 5%, suggesting that haemoconcentration had occurred during VIP infusion. Urine flow fell to about a third, and the fractional excretion of sodium, potassium, chloride and calcium fell to between half and two-thirds of control values. Fractional excretion of phosphate did not fall significantly. Plasma renin activity rose about 3-fold during VIP infusion.

Pentagastrin and cholecystokinin octapeptide (CCK8) were infused i.v. at three different doses in two sets of 4 conscious rabbits following a repeated measurements design (130, 1,300 and 13,000 pmol kg-1 min-1 pentagastrin; 5, 50 and 450 pmol kg-1 min-1 CCK8). In man, two different doses of pentagastrin (13 and 65 pmol kg-1 min-1) were infused in two groups of 6 subjects, and CCK8 (2 pmol kg-1 min-1) in a third group. According to published human postprandial levels, plasma CCK8-like immunoreactivity concentrations were supraphysiological at all doses infused. In the rabbit, pentagastrin produced a dose-related fall in urine flow and free water clearance, but no significant change in systemic and renal haemodynamics, electrolyte excretion and measured plasma constituents; however, in human subjects, pentagastrin increased renal sodium excretion and reduced potassium excretion but did not change glomerular filtration rate. In the rabbit, CCK8 produced a dose-related fall in plasma renin activity, plasma calcium concentration and mean arterial blood pressure; dose-dependent increases in effective renal plasma flow, glomerular filtration rate and renal sodium excretion. In man, changes in sodium and potassium excretion similar to pentagastrin were observed; there were no significant changes in plasma renin activity, plasma calcium concentration, blood pressure, effective renal plasma flow or glomerular filtration rate. The pharmacological renal effects of pentagastrin in conscious water-loaded rabbits resemble vasopressin. In contrast, CCK8's most striking effect was vasodilatation and was unusual in inhibiting rather than stimulating renin release. In man the net changes in urine composition found during infusion of these peptides are similar to those produced by the potassium-sparing diuretics, amiloride and triamterene. However the generally weak renal effects observed, even at pharmacological doses, indicate that these peptides are unlikely to influence renal function under normal physiological conditions.

1. An investigation was undertaken of the role of adrenergic influences on the transient change in colonic potential difference (p.d.) induced by handling in the rabbit. 2. P.d. was increased from 9-5 +/- 0-5 to 27-05 +/- 1-94 mV during a 2 hr period of handling and wrapping. Atropine and alpha-adrenergic block during this 2 hr period did not alter the magnitude of the response and the response in adrenalectomized animals was not significantly different from that of normal animals. 3. 'Total' adrenergic block and selective beta-adrenergic block abolished the change in p.d. with handling and infusion of an alpha-receptor agonist during the 2 hr period significantly reduced the response. 4. The changes in colonic p.d. with handling were greatly increased by the infusion of a beta-receptor agonist during the 2 hr test period. 5. The results indicate that the change in colonic p.d. with handling is a direct effect of the autonomic nervous system mediated via beta-receptors and that the changes were not related to the effects of circulating catecholamines or to changes in aldosterone production.

A relationship between salt intake and blood pressure has been described in cross-sectional studies of several populations. However, serious methodological problems in many studies could have resulted in erroneous results. In the present studies, the blood pressure profiles of a Kenyan tribe have been shown to differ according to environment, being lower in rural and higher in urban communities. Although several factors could explain the observed blood pressure differences, dietary factors, including sodium and potassium intake, could be important determinants of the observed differences. A within-population study of 1,737 rural male subjects was carried out in which it was found that systolic and diastolic pressures correlated positively with urinary sodium/potassium ratios. In this rural group, within subject day-to-day variations in dietary electrolytes are small, as indicated from multiple urinary collections, and are less than those observed in Western societies. We have demonstrated in this rural population that causal samples of urine correlated well with average sodium and potassium excretion over a 7-day period. Preliminary results are reported of a longitudinal study of migrants from a low to a high blood pressure environment and a nonmigrant population. The blood pressure rise consequent to migration was related independently to changes in body weight and urinary electrolytes. The implications of these observations for active intervention studies are discussed.

1. The influence of cyclic adenosine 3',5'-monophosphate (cyclic AMP), cylic guanosine 3',5'-monophosphate (cyclic GMP) and theophylline on renin secretion was examined in the isolated kidney of the rat perfused with Krebs dextran solution. 2. Neither cyclic AMP (10(-6) to 10(-4) M) nor dibytyryl cyclic AMP (10(-5) M) produced an increase in renin secretion. 3. Cyclic GMP and 8 Br-cyclic GMP caused a small rise in renin secretion in some experiments but this effect was independent of the dose and its physiological significance is uncertain. 4. Theophylline (10(-6) to 10(14) M) caused a significant elevation in renin secretion which was not blocked by (+)-propranolol. Theophylline with cyclic AMP or cyclic GMP did not produce an amplified effect. 5. Despite previous suggestions that cyclic AMP stimulated renin secretion, this could not be confirmed in the present preparation. Since there is no evidence that cyclic AMP or cyclic GMP (or their derivatives, dibutyryl cyclic AMP and 8 Br-cyclic GMP) enter the cells, it will be necessary to study their activity in isolated juxtaglomerular cells to define a possible role.

Retinal vein obstruction is a common complication of the retinopathy seen in patients with chronic hypertension. Previous studies have shown an abnormal control of intraocular pressure in response to changes of posture in patients with retinal vein obstruction. This paper describes the results of the investigation of the intraocular pressure response in 57 normotensive healthy adults and in 95 hypertensive patients, with a short study of 14 diabetic patients. Both hypertensive and diabetic groups showed abnormal responses. The possible significance of these findings as the expression of a fundamental anomaly by patients who develop either hypertension or diabetes is discussed.

The present study was undertaken to isolate and investigate some physicochemical properties of renin granules from the rat kidney cortex. Two preparations of subcellular organelles were used: a primary-granule fraction, which allowed the properties of lysosomes to be compared simultaneously with those of renin granules, and a semi-purified preparation of the latter. The specific activity of renin in the primary-granule preparations was about 4-fold higher than in the original homogenate; that of the semi-purified renin-granule preparation was about 18-fold higher than in the homogenate, and consisted mainly of electron-dense granules but some mitochondria were also observed. Renin and acid phosphatase release from the primary-granule preparation was increased by lowering osmolality, by a low-molecular-weight solute (glucose) and by Triton X-100 or digitonin. Enzyme release was decreased by lowering the incubation temperature (4 degrees C) or the presence of CaCl2. Renin release from the partially purified granule preparation was not affected by cyclic AMP, cyclic GMP and ATP.

Inhibition of renin secretion from incubations of rat kidney cortex by angiotensin II (AII), ouabain and K+ depletion, depended on the presence of external Ca2+. AII inhibition of isoprenaline-stimulated renin secretion was only partially dependent on external Ca2+. Ouabain and K+ depletion inhibited isoprenaline-stimulated renin release but only in the presence of external Ca2+. Since, in Ca2+-free medium, isoprenaline stimulated renin release when the Na+/K+-ATPase was blocked, isoprenaline probably does not act through the Na+/K+-ATPase. Lanthanum blocked the stimulation of renin release by isoprenaline. Ethylenediamine tetra-acetic acid (EDTA) and ethyleneglycol-bis-(beta-amino-ethyl ether) N,N'-tetra-acetic acid (EGTA) increased renin secretion to a similar degree in Ca2+- and Mg2+-free buffer. When Mg2+ was present the effect of EGTA, but not EDTA, was considerably reduced. Verapamil reduced the fall in basal renin secretion in normal but not Ca2+-free buffer. Verapamil did not block the inhibitory effects of AII or ouabain and did not alter the stimulation of renin secretion by isoprenaline. Bay K 8644 inhibited renin secretion from cortex incubated in medium containing 15 mM K+ and this was dependent on extracellular Ca2+. In normal buffer (5.9 mM K+) Bay K 8644 increased renin secretion.

Blood pressure (BP) and associated factors were determined in 1737 men in a remote Kenyan agricultural community. Systolic BP showed no significant rise with age until after 54 years; diastolic BP showed a small rise with age. Both systolic and diastolic BP correlated with weight independent of age. Systolic and diastolic BP correlated positively with casual urinary sodium/potassium and negatively with potassium/creatinine ratios. Both systolic and diastolic BP correlated significantly with the number of years of education, as did urinary sodium/potassium and sodium/creatinine ratios. Potassium/creatinine ratios were negatively correlated with the number of years of education. Blood pressure and urinary sodium/creatinine ratios were significantly lower in subsistence farmers compared with those in other occupations, and potassium/creatinine ratios were significantly higher. Two pilot studies of Luo tribesmen showed a strong correlation between casual urinary electrolyte ratios and those derived from 24-hour urine samples and a greater variance of sodium excretion between these people than that found within individuals. These results suggest that a relationship between BP and casual urine electrolyte estimations may be identifiable in communities where there is less day-to-day dietary variation. They also suggest that some of the changes in BP associated with urbanization could be mediated by changes in dietary electrolytes.

Conscious rabbits received either vasoactive intestinal polypeptide (VIP) at a dose of 1, 10 or 25 pmol kg-1 min-1 or vehicle alone (control) through an ear vein for 2 h. Experimental design followed a randomized Latin square arrangement. VIP led to a decrease in effective renal plasma flow and glomerular filtration rate (P less than 0.01) during infusion of the middle and high doses. Mean arterial blood pressure rose slightly (P less than 0.05) and filtration fraction increased (P less than 0.01) during infusion of the middle dose. The high dose produced a rise in heart rate, a fall in plasma sodium, potassium and phosphate concentrations and a rise in plasma solids (P less than 0.01). In spite of the renal haemodynamic effects and changes in plasma composition during infusion of the high dose, fractional excretion of sodium, potassium and chloride doubled (P less than 0.05), suggesting a direct action of VIP on renal tubular function. Plasma renin activity increased between 2- and 3-fold (P less than 0.01). The mechanism of the renin response is uncertain. These results, together with the reported presence of VIP-like material in the renal cortex, may indicate a role for VIP in the regulation of renal function, including renin release.

We have determined the haemodynamic responses to a balanced liquid meal in eight normal subjects, before and after administration of the somatostatin analogue, Octreotide (SMS 201-995), which inhibits the release of gastrointestinal peptides. In the absence of Octreotide ingestion of the meal caused a marked increase in superior mesenteric artery (SMA) blood flow. Blood pressure was maintained, presumably by a compensatory rise in cardiac output and forearm vascular resistance. After Octreotide there was a fall in SMA blood flow alone, with no further changes after food ingestion. We conclude that Octreotide prevents the haemodynamic changes following food ingestion, probably by inhibiting the release of those gastrointestinal peptides that induce splanchnic vasodilatation.

Following a random block experimental design in each case, three repeated measurement studies were carried out in three different groups of conscious rabbits, to investigate the renal effects of increasing doses of intravenous calcium chloride (CaCl2) and bovine parathyroid hormone (PTH). In the first study, each rabbit received either CaCl2 (0.15, 0.3, 0.5 or 1.0 mg kg-1 min-1) or vehicle alone (control) for 160 min. In the second study, rabbits were given either PTH (0.15 microgram kg-1 min-1), CaCl2 (1.0 mg kg-1 min-1), PTH plus CaCl2 (0.15 microgram kg-1 min-1 and 1.0 mg kg-1 min-1, respectively) or vehicle alone; PTH was infused for just over 60 min. In the third study, a much smaller dose (0.05 mg kg-1 min-1) of CaCl2 was infused for 100 min. CaCl2 infusion produced a striking fall in fractional excretion of sodium of at least 50% (P less than 0.01), but this was not dose related, being almost maximal at the smaller doses infused. Although this effect was evident in the absence of any changes in total plasma calcium concentration at the lower doses of CaCl2, renal calcium excretion was increased between 2- and 20-fold (P less than 0.01) at all doses infused. Fractional excretion of chloride doubled at the two higher doses of CaCl2 (P less than 0.01), but potassium excretion was unchanged. There were no consistent alterations in mean arterial blood pressure, effective renal plasma flow, glomerular filtration rate or plasma renin activity (PRA); total plasma calcium concentration was consistently elevated only during infusion of the high dose by just under 1 mmol l-1. PTH infusion had no measured effect on fractional excretion of sodium or renal calcium excretion, but doubled fractional potassium excretion (P less than 0.05). Heart rate and PRA increased (P less than 0.01 and less than 0.05, respectively), the latter by 50%, but systemic pressure and renal haemodynamics were not significantly affected. By contrast, PTH infused with CaCl2 produced a 4-fold rise in fractional sodium excretion and although renal calcium excretion remained increased, it was reduced by ca. 80% when compared with renal calcium excretion during infusion of CaCl2 alone. Infusion of PTH alone increased PRA, but when PTH and CaCl2 were infused together, PRA did not change.(ABSTRACT TRUNCATED AT 400 WORDS)

Twenty-four conscious male Wistar rats with hypertension induced by left renal artery clipping (two-kidney hypertension) were infused intravenously with 1-Sar-8-Ala-angiotensin II a competitive angiotensin II antagonist. The spectrum of responses was wide, ranging from a mild elevation in blood pressure to a marked fall in blood pressure, despite effective and specific angiotensin blockade in all cases. The change in blood pressure during 1-Sar-8-Ala-AII infusion activity showed a significant correlation with the level of plasma renin prevailing immediately before the infusion (r = - 0.78, P less than 0.01) but not with the prevailing blood urea level (r = 0.27, 0.1 greater than P greater than 0.05), the drgree of hypertension (r = 0.42, 0.1 greater than P greater than 0.05), or the time since clipping (r = 0.02, P greater than 0.05). There was no significant correlation between the degree of hypertension and the plasma renin activity (r = 0.42, 0.1 greater than P greater than 0.05). In rats with blood pressure drops greater than 20 mm Hg in response to 1-Sar-8-Ala-AII, the final blood pressure level was still above the normotensive range. Excision of the clipped kidney reduced blood pressure to normal or to near normal within 24 hours in all of the rats tested. It is concluded that the degree of dependence of renal hypertension on the renin-angiotensin system is directly related to the increase in circulating angiotensin itself and not to an increase in sensitivity to angiotensin. Other factors appear to be involved in renal clip hypertension in addition to circulating renin and angiotensin, especially when the measured activity of plasma renin is normal.

As part of a longitudinal study of migrants who move from a subsistence farming rural society to Nairobi, blood pressures and associated factors were measured in cross sectional studies of members of the Luo tribe in their traditional rural environment and in the urban environment of Nairobi. Blood pressures in Nairobi correlated with duration of urban residence. In the rural area men showed a negligible rise in blood pressure with age, and both sexes showed a significantly smaller rise than in the urban area. Although mean weights of the rural group were smaller, this did not account for all the urban/rural differences in blood pressures. Nevertheless, mean urinary sodium concentration and sodium ratios (sodium/potassium and sodium/creatinine) were significantly higher in the urban group whereas mean urinary potassium concentration and potassium/creatinine ratio were significantly lower. Perhaps the ratio of sodium to potassium in the diet contributes to the different blood pressure profiles of these two populations.

Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery. There was a highly significant fall in mean systolic and diastolic pressures after the operation. The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients. There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone.

Vasoactive intestinal polypeptide (VIP) has been found within the renal cortex and is believed to be a neurotransmitter. Although it produces systemic vasodilatation and renin release, the exact mechanism of the latter response is uncertain. When infused into conscious rabbits, VIP elicits a rise in plasma renin activity (PRA) and an increase in heart rate. The rise in PRA is unaltered by pretreatment with propranolol, but is attenuated by indomethacin. The tachycardia is inhibited by propranolol, but unaffected by indomethacin. We conclude that the renin response to VIP is in part prostaglandin-dependent and that the heart rate response is due to direct or reflex beta-adrenoceptor stimulation.

1. The acute reduction of renal blood flow following adrenalectomy in the rat, which had previously been shown to be associated with sequestration of blood volume in the splanchnic area, was further investigated. An attempt was made to define the role of the renal sympathetic nerves in causing the blood flow change. 2. The systemic and renal intra-arterial administration of phenoxybenzamine, isoprenaline and propranolol and denervation of the renal pedicle failed to re-establish normal renal function. 3. Infusion of P113 (sarcosyl1 alanine8), an angiotensin blocker, failed to improve renal function. 4. In contrast, volume replacement with high-molecular weight PVP caused a prompt increase of RPF and GFR without altering arterial pressure and central venous pressure. 5. Angiographic studies demonstrated that the calibre of the aorta of adrenalectomized rats was significantly smaller than that of the sham operated and increased after the administration of this plasma volume expander. 6. It was concluded that after adrenalectomy the major arteries readjusted their calibre to the reduced volume of blood in the arterial tree with maintenance of a constant pressure/volume relationship. Their contracted state in the case of the kidney then led to flow reduction.

Primary hyperaldosteronism is a potentially curable cause of hypertension, and much interest has been shown in methods of diagnosing the associated hypokalaemic hypertension and localising the adrenal adenoma. In two patients the diagnosis of primary aldosteronism was confirmed by colonic potential measurement and the adenoma localised by a new subtraction technique for early adrenal imaging applied to the use of 131I-19-iodocholesterol. Both patients underwent adrenalectomy and in each case an adenoma was removed. Blood pressure and electrolyte levels returned to normal after operation. In one patient bilateral adrenal phlebography had failed to show the tumour, and sampling of aldosterone concentrations in the adrenal veins had been unsatisfactory.

Eleven patients with a central retinal vein obstruction and 18 with tributary vein obstruction were examined. The intraocular pressure of both eyes of each subject was measured while he was in the sitting position and again after he had been lying down for 15 minutes. Tonography was then carried out on both eyes. No correlation was found between the value of the coefficient of outflow and the magnitude of the rise in intraocular pressure occurring in any eye on the adoption of the supine position, and no correlation between the relative values of the coefficients of outflow in any pair of eyes and the occurrence of the obstruction in one eye rather than the other.

The authors have used a sensitive alkaline phosphatase-anti-alkaline-phosphatase immunohistochemical method to examine 28 human pulmonary carcinomas for the presence of renin. Immunoreactive renin was found in 23 (82%) cases. Specific staining was always associated with small vessels in the stroma of the tumor or in adjacent areas of inflamed fibrous tissue. Within vessels, renin was localized in the cytoplasm of medial cells. Adenocarcinoma exhibited the most consistent staining (11/12 cases), and this appeared to be independent of the degree of tumor differentiation. Immunoreactive renin was also detected in squamous cell (7/8 cases), undifferentiated large cell (4/4 cases), and small cell undifferentiated carcinoma (1/1 cases), but the number of vessels and intensity of staining were usually less than seen in adenocarcinoma. Staining was not found in the bronchioloalveolar variant of adenocarcinoma (0/3 cases). By means of immunoaffinity chromatography with monoclonal antibodies (MAbs) raised to kidney renin, both active and inactive renin were extracted from homogenates of surgical specimens. The molecular weight of both forms of renin was approximately 59,000 daltons.

The effect of change of posture on the level of the intraocular pressure was studied in 22 patients who had suffered 'occlusion' of a central retinal vein, 14 patients with occlusion of a tributary of the central vein, and 23 normal subjects. The results showed a significant difference in behaviour between subjects in the control group and both groups of patients with retinal vein occlusions. In general it appears that the normal person maintains a relatively rigid control of ocular tension. The eyes are maintained at similar pressures which vary very little with change in posture. In contrast, the patient with a retinal vein occlusion (whether central or tributary) does not appear to have a similar degree of control. The eyes are not maintained at closely similar pressures, and each eye shows a change of pressure with change of posture which is considerably greater than that shown by the eyes of normal persons. The significance of these results is discussed with particular reference to the clinical association of retinal vein occlusion and chronic simple glaucoma, in which latter condition a similar lack of postural control of the intraocular pressure is found.

1 The effects of the disodium salt of ethylenediamine tetra-acetate (EDTA) and 1, 2, bis, 2 aminoethoxyethane-NNN'N'-tetra-acetic acid (EGTA) on renin secretion and vascular resistance were studied in the isolated perfused kidney of the rat. 2 Both substances produced a significant increase of renin release 3 In the absence of calcium and magnesium, EDTA still increased rein release and there was now a considerable increase of perfusion pressure. 4 The rise of pressure but not the rise of renin was inhibited by the removal of potassium from the perfusate when EDTA was administered in the absence of calcium. 5 Propranolol and phenoxybenzamine had no effect on the vasoconstrictor action of EDTA. 6 EGTA was less effective as a renin releaser than EDTA until magnesium was removed from the perfusate. Furter, it had only a small effect on perfusion pressure in contrast to EDTA.