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Hypertension causes marked adaptive changes in the cerebral circulation. The excess risk of stroke associated with hypertension is eliminated in controlled trials of antihypertensive treatment. Such treatment may even prevent transient ischaemic attacks in the elderly. In rare cases, overzealous antihypertensive treatment may cause cerebral ischaemia, especially in the initial treatment of very severe hypertension. Headache may occasionally be caused by severe hypertension, which may also lead to the rare syndrome of acute hypertensive encephalopathy. Finally, the importance of white-matter lesions, or leukoaraiosis, in hypertension is not yet fully established.

An earlier controlled trial showed that over an average of 26 months, enalapril slowed the progression of chronic renal failure. Following completion of the trial, the patients continued to receive antihypertensive treatment according to ordinary clinical criteria. All but four patients in the enalapril group remained on that drug, and two patients in the control group were switched to an angiotensin-converting enzyme (ACE) inhibitor. In the present study the fate of the 70 patients 44 months after termination of the trial was investigated, with a total follow-up of around 7 years. In the original enalapril group, 12 of the 35 patients (34%) were alive without renal replacement therapy versus five of the 35 patients (14%) in the control group. This difference of 20% in favour of having been in the enalapril group in the original trial was significant (P = 0.05; 95% confidence limits 0.5-39.5%). The influence of baseline proteinuria on clinical outcome was analysed. In the original control group, baseline renal clearances of albumin (Calb) and immunoglobulin G (CIgG) were significantly lower in patients surviving without renal replacement therapy at follow-up than in patients who ultimately developed end-stage renal failure (ESRF) (P < 0.05). In the original enalapril group, these baseline clearances were equal in the two renal outcome groups. In all patients, baseline Calb and CIgG were negatively correlated with the rate of change in GFR during the controlled trial (r = -0.37, P < 0.01 and r = -0.28, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Dietary supplementation with fish oil has been said to improve renal function in cyclosporin A (CsA)-treated subjects., Methods: Renal function and the acute renal haemodynamic and tubular response to an oral CsA-dose (3 mg/kg) were investigated before and after 12 weeks of fish oil supplementation (6 g/day) in 12 low-dose CsA-treated kidney-transplanted patients (s-creatinine, 124 +/- 24 mumol/l, mean +/- SD). After an overnight fast, ten l-h renal clearance periods were performed, two periods before and eight after CsA-ingestion. An additional control clearance study without CsA intake was performed in six subjects., Results: Fish oil did not change baseline values of the effective renal plasma flow (ERPF) or the glomerular filtration rate (GFR). Compared to the control study, CsA decreased GFR and ERPF significantly on average 20 +/- 3% (P < 0.01) and 23 +/- 3% (P < 0.01) respectively, 4-6 h after peak CsA blood concentration with no additional effect of fish oil. CsA also significantly decreased the renal clearance of lithium, used as an index of proximal tubular outflow, with no impact of dietary fish oil., Conclusion: Fish oil supplementation had no effect on baseline renal function or CsA-induced hypoperfusion in stable renal transplant recipients treated with a low maintenance dose of CsA.

Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

1. Glomerular filtration rate and sequential tubular function were investigated in 18 adult renal transplant recipients and in their matched, adult living-related kidney donors before and 5 days after transplantation/uninephrectomy. At day 54, 13 donors and 11 recipients were re-investigated. Sixteen of these constituted eight matched pairs. This reduction in the study population was caused by the application of two withdrawal criteria. 2. In the recipients glomerular filtration rate was unchanged at day 5 and had increased to 61 ml/min at day 54 (P < 0.05). In the donors glomerular filtration rate had increased to 59 ml/min by day 5 (P < 0.01) and was unchanged at day 54. 3. In the recipients lithium clearance was unchanged at day 5 and had increased to 23 ml/min at day 54 (P < 0.01). In the donors the lithium clearance had increased by day 5 (P < 0.01). 4. In the recipients the absolute proximal fluid reabsorption rate was about 36 ml/min throughout the study period. In the donors the absolute proximal fluid reabsorption rate had increased to 42 ml/min by day 5 (P < 0.05) and increased further to 44 ml/min by day 54 (P < 0.01). 5. In the recipients sodium clearance increased from 0.54 ml/min to 2.10 ml/min at day 54 (P < 0.01). In the donors it increased from 0.64 ml/min to 0.99 ml/min at day 54 (P < 0.05). 6. Donor-recipient comparison showed that at day 54 there was no significant difference with regard to glomerular filtration rate, lithium clearance, absolute and fractional proximal fluid reabsorption rate and absolute distal sodium reabsorption rate.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Previous histological studies have demonstrated partial reinnervation of the human transplanted kidney. However, it remains unknown whether this reinnervation is of any functional significance. 2. The effects of noradrenaline infusion (2 micrograms h-1kg-1) and lower body negative pressure (-27 mmHg) on renal haemodynamics, sodium excretion and tubular function were investigated in 25 renal transplant recipients and 10 normal subjects. Sixteen of the transplant recipients had all been transplanted for more than 27 months, and nine had all been transplanted for less than 2 months. 3. After an overnight fast, the subjects were water-loaded, and clearance studies were performed with a 1 h baseline period, a 1 h period with noradrenaline infusion, another 1 h baseline period, and a final 1 h period with lower body negative pressure. 4. During noradrenaline infusion the relative decrease in effective renal plasma flow, glomerular filtration rate and clearance of lithium and sodium was significantly more pronounced in the long-term transplanted patients than in the control subjects. 5. Lower body negative pressure only depressed the glomerular filtration rate significantly in the control subjects. Further, the relative decrease in effective renal plasma flow and clearance of lithium and sodium was significantly greater in the control subjects than in the two groups of transplanted patients. 6. The present study thus demonstrated that in short- and long-term transplanted kidneys in man, supersensitivity to circulating noradrenaline and an inadequate response to lower body negative pressure was present. This strongly suggests that the human transplanted kidney remains functionally denervated.

The present study investigated the contribution of adrenergic beta 1-receptor stimulation to the cardiovascular and renal effects of low-dose dopamine in eight normal, water-loaded humans. Metoprolol (100 mg) or placebo was administered orally at 08.00 h in a randomized, double-blind fashion on two different days. Renal clearance studies were performed during a 1 h baseline period, two 1 h periods with dopamine infusion (3 micrograms kg-1 min-1), and a 1 h recovery period. Cardiac output was measured by an ultrasonic Doppler method, and lithium clearance (CLLi) was used to estimate proximal tubular outflow. Baseline values of heart rate, systolic pressure and mean arterial pressure decreased with metoprolol compared with placebo, but cardiac output, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were not significantly changed. Metoprolol significantly decreased baseline CLLi and sodium clearance (CLNa) by 19% (P < 0.01) and 34% (P < 0.01), respectively. Metoprolol blunted the dopamine-induced increases in heart rate and systolic pressure, but cardiac output increased to the same extent on both study days by 26% (placebo, P < 0.05) and by 31% (metoprolol, P < 0.01), respectively. With and without metoprolol, dopamine did not significantly change GFR, and the percentage increases in ERPF were similar on the two study days (40% (P < 0.001) and 42% (P < 0.001), respectively). Dopamine increased CLLi and CLNa by 31% (P < 0.01) and 114% (P < 0.01), respectively, with placebo, and by 36% (P < 0.01) and 114% (P < 0.01), respectively, with metoprolol. Values during infusion remained significantly lower with metoprolol compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral blood flow (CBF) and cerebral metabolic activity tend to decrease in old age. The effect of age per se on the regulation of CBF is not readily separated from the effect of age-associated diseases such as atherosclerosis, multi-infarct dementia, and diabetes mellitus, which may lead to an impairment of CBF autoregulation. Stroke may be prevented effectively by antihypertensive treatment in otherwise healthy elderly patients, but care should be taken to prevent overtreatment with consequent cerebral ischemia. The risk of this may be especially great in elderly patients with hypertension who have postural hypotension.

In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomised in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least two years or until they needed dialysis. The therapeutic goal, was a blood pressure of 120 ti 140/80 to 90 mmHg. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month, and in the control group, it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (p < 0.05). There was no significant difference in blood pressure between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy.

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 micrograms min-1 kg-1) was investigated in 12 healthy males. In a double-blind and randomized design, 450mg or 600mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium it increased to 1.25 +/- 0.44 (P < 0.001) and 1.17 +/- 0.46 ml/min (P < 0.01) after 450 and 600mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% (P < 0.05) and 10% (P < 0.01), respectively. 3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450mg (P < 0.01) and 600mg (P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conventional antihypertensive treatment. The patients were followed for at least 2 years or until they needed dialysis. The groups were comparable with respect to age and sex distribution, etiology of renal diseases, initial levels of renal function and arterial blood pressure (BP), and protein intake. The therapeutic goal was a BP of 120 to 140/80 to 90 mm Hg. The GFR, estimated by the plasma clearance of 51Cr-EDTA, was measured every third month, and the individual rate of progression was calculated as the slope of the GFR v time plot. In the enalapril group, the median decline in GFR was -0.20 (range, +0.18 to -7.11) mL/min/1.73 m2/month and in the control group it was -0.31 (+0.01 to -1.97) mL/min/1.73 m2/month (P less than .05). There was no significant difference in blood pressure or plasma lipid levels between the groups. Thus, the progression of moderate to severe chronic nephropathy was slower on a basic treatment with enalapril as compared to conventional antihypertensive therapy.

A review is given of the normal regulation of cerebral blood flow (CBF) and its pathophysiology in hypertension and stroke. In otherwise healthy hypertensive patients, the absolute level of CBF is the same as in normal subjects. CBF autoregulation, however, is shifted towards higher pressure, thus impairing the tolerance to hypotension. In most patients, this does not interfere with the beneficial effect of treatment, i.e., stroke prevention. Cerebral ischemia, however, may be provoked by overzealous pressure lowering in selected clinical settings: initial or intensified treatment of very severe hypertension, treatment of hypertension in the elderly, and treatment of hypertension in acute stroke. In the latter, a complicated sequence of brain ischemia and hyperemia makes antihypertensive intervention difficult in the early phase, when blood pressure is probably best allowed to decrease spontaneously.

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (Nx) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of 51Cr-EDTA, lithium, sodium, potassium, and albumin. ANP was 7.4 +/- 3.1 pmol l-1 (mean +/- SD) before Nx and 8.7 +/- 6.1 pmol l-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45 +/- 7 ml min-1 before Nx to 57 +/- 8 ml min-1 (p less than 0.01), lithium clearance had risen from 13 +/- 2 ml min-1 before Nx to 20 +/- 7 ml min-1 (p less than 0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.

The subject of the cerebral circulation in the elderly is reviewed. In old age, cerebral blood flow (CBF), which is closely coupled to cerebral oxidative metabolism, decreases along with the amount of brain tissue. In healthy old people, the cerebral circulation is regulated as earlier in life, by autoregulation, metabolic regulation, and chemical and other factors. CBF and its regulation is influenced by disease processes prevailing in old age, such as dementia, atherosclerosis, diabetes mellitus, stroke, and hypertension. Hypertension, apart from being a risk factor for stroke, causes adaptive cerebral vascular changes, leading to a shift of the lower limit of autoregulation towards high pressure, with an impaired tolerance to pressure decrease. In old age, this adaptation may not be reversible. With this background, a conservative approach to elderly hypertensive patients is suggested, aimed at some reduction of pressure but carefully avoiding overtreatment.

Autoregulation of blood flow denotes the intrinsic ability of an organ or a vascular bed to maintain a constant perfusion in the face of blood pressure changes. Alternatively, autoregulation can be defined in terms of vascular resistance changes or simply arteriolar caliber changes as blood pressure or perfusion pressure varies. While known in almost any vascular bed, autoregulation and its disturbance by disease has attracted particular attention in the cerebrovascular field. The basic mechanism of autoregulation of cerebral blood flow (CBF) is controversial. Most likely, the autoregulatory vessel caliber changes are mediated by an interplay between myogenic and metabolic mechanisms. Influence of perivascular nerves and most recently the vascular endothelium has also been the subject of intense investigation. CBF autoregulation typically operates between mean blood pressures of the order of 60 and 150 mm Hg. These limits are not entirely fixed but can be modulated by sympathetic nervous activity, the vascular renin-angiotensin system, and any factor (notably changes in arterial carbon dioxide tension) that decreases or increases CBF. Disease states of the brain may impair or abolish CBF autoregulation. Thus, autoregulation is lost in severe head injury or acute ischemic stroke, leaving surviving brain tissue unprotected against the potentially harmful effect of blood pressure changes. Likewise, autoregulation may be lost in the surroundings of a space-occupying brain lesion, be it a tumor or a hematoma. In many such disease states, autoregulation may be regained by hyperventilatory hypocapnia. Autoregulation may also be impaired in neonatal brain asphyxia and infections of the central nervous system, but appears to be intact in spreading depression and migraine, despite impairment of chemical and metabolic control of CBF. In chronic hypertension, the limits of autoregulation are shifted toward high blood pressure. Acute hypertensive encephalopathy, on the other hand, is thought to be due to autoregulatory failure at very high pressure. In long-term diabetes mellitus there may be chronic impairment of CBF autoregulation, probably due to diabetic microangiopathy.

The effect of the angiotensin converting enzyme (ACE) inhibitor fosinopril sodium on regional cerebral blood flow (rCBF) was investigated in 8 patients with moderate essential hypertension. A constant dose of chlorthalidone (25 mg/day) was given to stimulate the renin angiotensin system, and fosinopril sodium was given in incremental doses (10 to 40 mg/day) with the aim of obtaining a diastolic blood pressure at or below 90 mm Hg. Regional CBF was measured with xenon-133 inhalation tomography. Repetitive measurements were made at the start of treatment and again after 4 to 12 weeks treatment in the resting supine position, and during lower body negative pressure (LBNP) as a substitute for the upright position. Four hours after the first 10 mg dose of fosinopril the mean arterial pressure (MAP) had been reduced from 127 +/- 13 mm Hg to 105 +/- 9 mm Hg (P less than .01) without any significant change in mean CBF (55 +/- 9 mL/(100 g X min) at baseline versus 52 +/- 9 mL/(100 g X min) after fosinopril). After prolonged treatment with chlorthalidone and fosinopril, mean CBF was still unchanged from baseline levels, when measured 4 and 24 h after a single dose of fosinopril, despite a 10% reduction in MAP (P less than .01). LBNP did not lead to any significant change in rCBF. The regional distribution of CBF was normal in all patients throughout the study. We conclude that treatment with fosinopril sodium causes a moderate fall in blood pressure without any adverse effects on rCBF.

Angiotensin converting enzyme (ACE) inhibitors has been suggested to halt the progression of chronic renal failure. As the initial step of a controlled trial of this hypothesis, it was investigated whether start of enalapril in patients with severe chronic nephropathy might cause a critical fall in their renal function. Thirty-one patients were studied, 26 on chronic antihypertensive treatment with drugs other than ACE inhibitors and 5 untreated normotensive. 51Cr-EDTA plasma clearance and renal technetium-99m dimercaptosuccinic acid (99mTc-DMSA) scintigraphy were made before and 24 h after start of enalapril, mean dose 9 mg. Blood pressure fell from median 148/88 to 119/78 mmHg (p less than 0.01). Glomerular filtration rate (GFR) fell from median 14 to 12 ml/min/1.73 m2 (p less than 0.01). The median change in GFR was -14% (range -44% to +10%). The split renal function was unchanged and the scintigrams showed no intrarenal activity defects. In conclusion, enalapril caused a fall in GFR, which was clinically acceptable in most of the patients.

Therapeutic intervention in acute ischemic stroke must be directed at salvaging damaged, but viable, tissue. Ideally, treatment should start in the initial phase when the ischemic tissue still retains a potential for recovery. Furthermore, ischemic stroke may be associated with "chronic threatening ischemia," in which there is ischemic, but viable, tissue with collateral circulation distal to a stenosed or occluded artery. In chronic threatening ischemia, therapeutic manipulation may improve the clinical situation. Since cerebral vasomotor function is impaired or abolished in acute stroke and chronic threatening ischemia, vasodilator therapy tends to "steal" blood away from the lesion. Vasoconstrictors, by decreasing perfusion in healthy parts of the brain, may improve perfusion in ischemic tissue; it has, however, proved difficult to gain clinical benefit from this therapeutic modality. Converting-enzyme inhibitors may have a place in the management of ischemic stroke as they tend to shift cerebral autoregulation toward lower pressures. Calcium antagonists given acutely in stroke may create a steal effect. Despite this, clinical trials indicate that calcium-antagonist treatment may improve the outcome of stroke patients, possibly by an action on the ischemia-threatened brain cells.

Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51Cr-EDTA plasma clearance fell by 14% (P less than 0.01), but renal uptake of 99mTc-DMSA increased by 10% (P less than 0.01). It is concluded that DMSA in chronic renal failure is mainly taken up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR.

Autoregulation of the cerebral circulation is the regulating mechanism that keeps cerebral blood flow (CBF) constant within wide limits of arterial pressure. The lower limit is defined as the value of mean arterial pressure below which CBF decreases below the plateau, and the upper limit as the value of mean arterial pressure above which CBF increases above the plateau (60 and 150 mm Hg, respectively). Two possible mechanisms for autoregulation are discussed, myogenic response and metabolic regulation. Stimulation of the sympathetic nervous system and antagonism of the renin-angiotensin system modulate CBF autoregulation by shifting the entire curve toward higher or lower values of arterial pressure, respectively. The autoregulatory curve is shifted toward higher arterial pressures in chronic hypertension. Therefore, the tolerance to acute decreases in arterial pressure is impaired. Concomitantly, the tolerance of the brain to acute increases in arterial pressure is improved. This shift in the limits of autoregulation is due to structural and functional (hemodynamic) changes in the cerebral resistance vessels. These adaptive changes are partly reversible after chronic treatment with antihypertensive agents. The pathophysiology of autoregulation should be taken into consideration before drugs are used to decrease arterial pressure acutely.

Eight patients with chronic glomerulonephritis were treated with either naproxen or sulindac in an open randomized study to observe their effects on the urinary excretion of prostaglandins and renal function. Both drugs were given for 7 days. Naproxen caused a decrease (p less than 0.01) of 80% in prostaglandin PGE2 and decrease (p less than 0.01) of 55% in prostaglandin PGF2 alpha. Sulindac caused a decrease (p = 0.01) of 37% in PGE2 and a decrease (p less than 0.05) in PGF2 alpha of 13%. The decrease in urinary excretion of prostaglandins were greater (p less than 0.05) during the naproxen treatment. Naproxen caused a decrease (p less than 0.05) in 24-hour creatinine clearance of 14 ml/min, an increase (p less than 0.05) in plasma urea of 1.0 mmol/l, an increase (p less than 0.05) in plasma potassium of 0.4 mmol/l and a decrease (p less than 0.01) in 24-hour urinary excretion of albumin of 11 mumol. Sulindac did not change any of these parameters significantly. In conclusion, sulindac affects renal prostaglandin synthesis to a significantly minor degree than naproxen and contrary to naproxen it does not influence the renal function in patients with chronic glomerular disease.

Infarct kidney hypertension was induced in congenital athymic nude rats and in their haired normal littermates. In both groups a significant and similar elevation of blood pressure was observed. The mesenteric vessels were studied histologically five, 12 and 20 days after operation. Necrotizing vasculitis with and without perivascular inflammatory reactions was found in mesenteric arteries and arterioles in six out of six athymic and in six out of 11 control rats. In sham operated athymic rats and in haired littermates neither hypertension nor vasculitis was observed. These observations indicate that the thymus play no role in the pathogenesis of acute hypertensive vascular disease.

The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with renal and spontaneous hypertension. Diazoxide (5 mg/kg, i.v. bolus), caused arterial pressure to fall rapidly to that of normotensive rats, i.e. c. 75 mmHg. There was a concomitant fall in cerebral blood flow of about 35% (P less than 0.01) in renal hypertensive rats and 25% (P less than 0.05) in spontaneously hypertensive rats; the greater fall in flow in the former corresponded to a greater drop in pressure. Flow remained at these reduced levels during a 2 h observation period. Histological examination revealed small areas of ischaemic damage in the brains of five of the twelve animals. In control hypertensive rats not given diazoxide, cerebral blood flow and blood pressure were stable during a 2 1/2 h period and there was no evidence of ischaemic damage to the brains. The diazoxide-induced reduction in cerebral blood flow was interpreted as being secondary to a blood pressure fall to below the lower limit of cerebral blood flow autoregulation. No evidence was found of direct effects on the cerebral circulation such as seen with ganglionic blockers, alpha-blockers and cerebral vasodilators.

In the years 1977 to 1981, 47 cases of phaeochromocytoma and 19 cases of aldosterone-producing adrenal adenoma (Conn's syndrome) were diagnosed in Denmark as reported to the National Register of Hospital Patients. This corresponds to an average annual incidence of phaeochromocytoma and Conn's syndrome of 1.9 and 0.8 per million inhabitants, respectively. Treatment results were evaluated from the patient's records and follow-up questionnaires. Of 30 surviving patients operated upon for phaeochromocytoma and followed-up after 18-81 months, 23 were normotensive without treatment and seven were mildly to moderately hypertensive. Of 11 patients operated upon for Conn's syndrome, follow-up data at 1-2 years were obtained in seven, of whom five were normotensive and two hypertensive. Phaeochromocytoma and Conn's syndrome are rare diseases. The results of surgical treatment are often gratifying, but not all patients remain normotensive after surgery, even in the absence of recurrence of endocrine disease.

The effect of chronic hypertension on cerebral blood flow (CBF) was studied in anaesthetised rats. CBF was measured with the intracarotid 133Xe injection method. Rats with spontaneous and renal hypertension were compared with normotensive controls. The lower limit of autoregulation was determined during controlled haemorrhage. In the normotensive rats, CBF remained constant until mean arterial pressure (MAP) had decreased to the range of 50-69 mm Hg. Thereafter, CBF decreased with each further decrease in MAP. In both types of hypertensive rats, CBF remained constant until MAP had decreased to the range of 70-89 mm Hg. Thus, a 20-mm Hg shift of the lower limit of CBF autoregulation was found in both spontaneous and renal hypertensive rats. A neuropathological study revealed ischaemic brains lesions in half of the hypertensive rats following hypotension, whereas only a single lesion was found in one of six normotensive rats. No ischaemic brain lesions were found in a control study in which CBF was shown to be stable over a 21/2-h period. In conclusion, hypertensive rats showed a shift of the lower limit of CBF autoregulation as well as an increased susceptibility to ischaemic brain damage during hypotension. These findings presumably reflect hypertensive structural changes in the cerebral circulation.

The blood-brain barrier permeability to captopril, and the cerebrovascular effects of intracerebroventricular administration of captopril, were studied in normotensive Wistar rats. The blood-brain barrier permeability-surface area product (PS), determined by an integral-uptake method, was about 1 X 10(-5) cm3/g/s in all brain regions studied. This was three to four times lower than the simultaneously determined PS of Na+ and Cl-, both of which are known to have very low blood-brain barrier permeability. Cerebral blood flow, determined by the intra-arterial 133xenon injection method, was unaffected by intracerebroventricular administration of 100 micrograms captopril. Furthermore the lower limit of cerebral blood flow autoregulation during haemorrhagic hypotension was also unaffected, being in the mean arterial pressure range (50-69 mmHg) in both controls and captopril-treated rats. It was concluded that the blood-brain barrier permeability of captopril was negligible and that inhibition of the brain renin-angiotensin system has no effect on global cerebral blood flow. The cerebrovascular effects of intravenously administered captopril (a resetting to lower pressure of the limits and range of cerebral blood flow autoregulation) are probably exerted via converting enzyme on the luminal surface of cerebral vessels.

Cerebrovascular reactivity to CO2 inhalation and voluntary hyperventilation was studied in seven normotensive subjects and nine hypertensive patients without clinical or angiographical signs of arteriosclerosis. Cerebral blood flow (CBF) was measured by the intracarotid 133Xe clearance method and calculated as the initial slope index. Three to five CBF measurements were made in each patient in the PaCO2 range of 20 to 55 mm Hg. No difference was observed in reactivity between hypertensive and normotensive patients, either during CO2 inhalation or during hyperventilation. The shape of the CBF:PaCO2 curve suggested a decrease in reactivity below a PaCO2 of 30 to 35 mm Hg in both groups. Above a PaCO2 of 35 mm Hg, exponential regression analysis yielded a mean reactivity of 6 +/- 2%, whereas below a PaCO2 of 30 mm Hg it was about 2%. The rise in CBF during CO2 inhalation was not influenced by the intravenous infusion of a small dose of trimethaphan which blocked the concomitant rise in blood pressure.

A 17-year-old girl with a severe pure red cell aplasia (PRCA) and an appropriate elevation of erythropoietin titres was treated successfully with plasmapheresis, during which plasma was exchanged with human albumin and Ringer lactate. Before this treatment, therapeutic attempts with prednisolone, oxymetholone and infusions with fresh frozen plasma had all been without effect. Bone marrow culture studies revealed an inhibitory activity against BFU-E in the plasma, an activity which could not be demonstrated after the plasmapheresis. 22 months after the plasmapheresis the patient is still healthy without any medication. This case adds additional evidence for the presence of a pathogenetic erythroid inhibitory factor in the plasma of some patients with PRCA.

When patients with functional unilateral renal artery stenosis are treated with an angiotensin I converting enzyme inhibitor (ACE-inhibitor) a risk is present for loss of the function of the affected kidney without clinical symptoms. Renal function should therefore be controlled in these patients before and after initiation of the treatment. Even a slight increase in serum creatinine must be followed by reassessment of the treatment and investigation for renocascular hypertension must be considered.

It is proposed that differences in autoregulatory reserve and blood oxygen extraction potential between the coronary and cerebral circulations explain why antihypertensive treatment effectively protects patients against stroke but has failed to reduce the increased incidence of myocardial infarction associated with hypertension. In the brain, oxygen extraction from the blood can be increased if blood pressure falls below the lower limit of autoregulation. In the coronary circulation, however, oxygen extraction is nearly maximum at rest, and lowering of blood pressure by antihypertensive therapy can lead to myocardial ischaemia.

The effect of captopril on cerebral blood flow (CBF) and its autoregulation was studied in spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Wistar rats. CBF was measured by the intracarotid 133Xe injection method. In one study 1 and 10 mg/kg captopril respectively were given intravenously to SHR and WKY. This caused the blood pressure to fall transiently below the lower blood pressure limit of CBF autoregulation; nonetheless CBF remained normal during captopril induced hypotension. In a second study it was shown with an integral uptake method that captopril is a very poor penetrator of the blood-brain barrier. In a third study captopril was instilled intracerebroventricularly in Wistar rats without any effect on CBF or its autoregulation. Thus when given intravenously, but not intracerebroventricularly captopril caused cerebral vasodilatation during acute hypotension.