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Body mass index and the risk of development of end-stage renal disease in a screened cohort.BackgroundObesity is associated with proteinuria and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined the significance of body mass index (BMI) as a risk factor for the development of ESRD in the general population.MethodsWe examined the relationship between BMI and the development of ESRD using data from a 1983 community-based screening in Okinawa, Japan. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry. BMI data were available for 100,753 screenees (47,504 men and 53,249 women) aged ≥20years. The cumulative incidence of ESRD was analyzed according to the quartile of BMI

This study was undertaken to compare age-related changes in endothelium-dependent vascular responses in both hypertensive and normotensive rats. Aorta from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) aged 4-6 weeks (young), 3-6 months (adult), and 12-25 months (old) were examined for relaxation to acetylcholine, adenosine 5'-triphosphate (ATP), and sodium nitroprusside. Rubbed (endothelium denuded) aorta from all groups displayed neither relaxation nor contraction to acetylcholine. Maximal relaxation responses to acetylcholine were reduced progressively with increasing age in unrubbed aorta of both SHR and WKY rats. In addition, acetylcholine caused not only dose-dependent relaxations at lower concentrations but also increases in tension at higher concentrations in unrubbed aorta of old WKY rats as well as adult and old SHR. However, indomethacin completely inhibited the tension development. As a result, aorta treated with indomethacin demonstrated similar acetylcholine-induced, endothelium-dependent relaxations in all groups. The thromboxane A2 synthetase inhibitor (E)-7-phenyl-7-(3-pyridyl)-6-heptanoic acid (CV-4151) partially but significantly depressed the increases in tension in aorta of old WKY rats. The degrees of endothelium-dependent relaxations to ATP and endothelium-independent relaxations to sodium nitroprusside were almost similar in all groups. These findings suggest that the release of or vascular responsiveness to endothelium-derived relaxing factor in the aorta is well maintained through senescence in both strains and that, in the aorta of not only SHR but also old normotensive WKY rats, the endothelium releases contracting factors that may be thromboxane A2 and other vasoconstrictor prostanoids.

Effects of 6-hydroxydopamine (6-OH-DA) injected into the lateral brain ventricle on the carotid sinus baroreceptor reflex were studied in rabbits anesthetized with alpha-chloralose and urethane. As short term effects, injection of 500 mug/kg of 6-OH-DA caused a fall in blood pressure and heart rate, enhanced the depressor and bradycardia responses to electrical stimulation of the carotid sinus nerve (CSN), and inhibited the pressor response to carotid occlusion. These effects reached the maximum with 2 hrs and disappeared by the 4th hr. Intraventricular injection of noradrenaline (NA) could mimic most of these effects. At 4.5 hrs after injection of 6-OH-DA, NA content of the brain was definitely reduced: 21% of control in the hypothalamus and 14% in the pons-medulla. Rabbits treated with 6-OH-DA under penthobarbital anesthesia 24 hrs before showed a slight fall in resting blood pressure and almost normal baroreceptor function. Intraventricular application of phentolamine abolished the responses to CSN stimulation in 6-OH-DA pretreated as well as normal animals. These results suggest that the acute effects of 6-OH-DA are based on the increased release of NA from the affected nerve terminals and that noradrenergic neurons are involved in the central pathway of baroreceptor reflex. Moreover, the relfex may be functionally maintained by a small portion of brain NA content, even when noradrenergic neurons are greatly affected by 6-OH-DA.

Responses to the changes in dietary sodium and posture were investigated in 9 young clinically healthy Japanese males who customarily consumed a larger amount of salt than North Americans or Europeans of mixed white ethnic background. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary aldosterone excretion rate (AER) differed at each end of 3- to 4-day spans on a "control", a high-salt and a low-salt diet and of furosemide administration. PRA and PAC, also determined during the upright position following the supine blood sampling, increased after only 1 hour of standing in each condition (p less than 0.05 or more). PRA and PAC were well correlated in all 4 conditions, regardless of the posture (r = 0.806, p less than 0.001). There were also highly significant correlations between the "supine" PRA or PAC and the preceding 24-hour AER (r = 0.869, p less than 0.001) for PRA; r = 0.855, p less than 0.001 for PAC). Correlation coefficients between PRA and PAC in 9 individual subjects ranged from 0.823 to 0.987. The estimates of constant and slope of the regression line between PRA and PAC varied from subject to subject. The renin-aldosterone axis in response to changes in dietary sodium and posture must be individually assessed.

We evaluated the time course of changes in the relative contribution of arginine-vasopressin (AVP) and sympathetic nervous system (SNS) during the development of DOCA-salt hypertension in rats. Intravenous administrations of an AVP antagonist (d(CH2)5Tyr(Me) AVP; AVPA) and hexamethonium (C6) were given at 3 and 7 days, and 2 and 4 weeks after the initiation of treatment with DOCA-salt to conscious and unrestrained rats. Mean arterial pressure (MAP) was higher and heart rate (HR) tended to be rapid in the rats on DOCA-salt treatment for over 1 week, compared with those of the control groups. The hypotensive effect of AVPA in the DOCA-salt treated rats was gradually enhanced with the development of hypertension and was significantly greater than in the control rats, at all stages of hypertension, including the prehypertensive phase. The depressor response to intravenous C6 following AVPA also resulted in a gradual enhancement, with time, after DOCA treatment. This decrease in MAP was greater at the hypertensive stage than that in the control rats, although the response was not significantly different among three groups on the 3rd treatment day. It was concluded that the pressor systems AVP and SNS may contribute to the initiation and development as well as maintenance of DOCA-salt hypertension in rats.

We evaluated the mechanisms of pressor responses to hypertonic NaCl administered intracisternally (IC) to conscious normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Both mean arterial pressure (MAP) and heart rate (HR) increased immediately after IC NaCl (1.5mol/l, 60 microliters/kg), but MAP returned rapidly to the basal level. Pressor and tachycardic actions at the early phase were mostly abolished by either hexamethonium or phentolamine with the blockade of sympathetic nervous system (SNS), and slightly diminished by the V1-vasopressin blocker. In contrast, at the following phase pressor responses were not suppressed by combined or solitary blockade of SNS, vasopressin and angiotensin II (AII). The pressor effects of IC NaCl were slightly greater in SHR than in WKY. It is concluded that the early-phase increases in MAP by hypertonic NaCl administered IC to conscious SHR and WKY may be attributed mainly to the increased activity of SNS and partly to the increased release of AVP, although the late- phase pressor responses may result from some pressor factor(s), unrelated to SNS, AVP and AII.

Under various conditions of sodium balance, 1-sarcosine-8-isoleucine angiotensin II was infused into 15 normotensive controls and 82 patients with benign essential hypertension. Changes in mean blood pressure induced by the analogue were correlated with the logarithm of plasma renin activity (r = -0.763, p less than 0.001 for the controls; r = -0.776, p less than 0.001 for the patients). Although the coefficients of determination were much the same, 0.95 confidence limits of the regression line did not overlap at renin levels over 7 ng/ml/h. At those levels, a decrease in the mean blood pressure induced by the analogue was greater in the hypertensive patients. A pressure-renin index was defined as a product of the logarithm of plasma renin activity and the mean blood pressure measured before the analogue infusion. The correlation between the analogue effect and the pressure-renin index was highly significant (r = -0.763, p less than 0.001 for the controls; r = -0.777, p less than 0.001 for the hypertensive patients). The regression line (0.95 confidence limit) for the hypertensives coincided with that for the normotensives. Thus, the blood pressure level should be taken into account when attempting to evaluate plasma renin activity.

A 55-year-old man with normotensive primary aldosteronism, hypopituitarism, epilepsy, and medullary sponge kidney is reported. Seventeen years before admission, he had been noted to have hypokalemia associated with high potassium clearance, suppressed plasma renin activity, metabolic alkalosis, and normal blood pressure as well as low urinary excretion of 17-hydroxycorticosteroids. He kept normotensive in spite of hyperaldosteronism until nine months after the initiation of replacement therapy with glucocorticoid and thyroxine for hypopituitarism, when he became hypertensive. Hypopituitarism seemed to play a role in keeping a normal blood pressure despite long-standing hyperaldosteronism.

SUMMARY:The effects of bilateral common carotid artery occlusion en brain metabolism and arterial acid-base balance were studied in normotensive and experimental renovascular hypertensive rats.One hour after carotid occlusion in hypertensive rats, supratentorial lactate increased to 383% and lactate-pyruvate ratio to 280% of the controls, while adenosine triphosphate (ATP) decreased to 69%. These metabolic changes were thought to be due to cerebral ischemia. Arterial pC02 was lowered and the pH was raised in the hypertensive animals due to cerebral ischemia induced hyperventilation. In the normotensive rats, carotid occlusion had minimal effects on cerebral metabolism and arterial acid-base balance.These results suggest that hypertensive rats are more susceptible to cerebral ischemia caused by carotid occlusion than normotensive rats. Increased cerebrovascular resistance in hypertension is discussed as a casual factor in cerebral ischemia.

1. The role of the sympathetic nervous system and the effect of vasopressin (AVP) on the hypotensive action of nifedipine (Nf) were evaluated in conscious, unrestrained normotensive and DOCA–salt hypertensive rats. 2. The hypotensive response to Nf was much greater in DOCA rats than in the controls. 3. Solitary blockade of the sympathetic nervous system or AVP, did not alter the Nf effect in either DOCA or control rats. However, a combination clearly diminished the effect of Nf in the DOCA group, but enhanced it in the controls. The inhibition of angiotensin II (ANG II) augmented the hypotensive effect of Nf in control animals, but not in the DOCA rats. The percentage fall in blood pressure with Nf was much the same in both groups after the combined inhibition of the sympathetic nervous system and AVP. 4. The enhanced hypotensive action of Nf in DOCA rats may be dependent on the hyperactivity of the sympathetic nervous system and AVP, which facilitates calcium influx, and in the normotensive animals the depressor response to Nf may relate to blockade of the calcium influx, independent of the sympathetic nervous system, AVP and ANG II.

We evaluated the effects of ageing and hypertension on endothelium-dependent relaxation and contraction of vascular smooth muscles. Aortic rings with and without endothelium from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), divided into young, adult and old groups, were examined for relaxation in response to acetylcholine, adenosine triphosphate (ATP) and sodium nitroprusside. Relaxation responses to acetylcholine and ATP in SHR were either equal to or greater than those in WKY. Relaxations induced by ATP were not altered by ageing, while the degree of acetylcholine-induced endothelium-dependent relaxations was in an inverse order of age in both SHR and WKY. In old SHR and WKY and adult SHR, lower doses of acetylcholine caused relaxations, but increases in the dose of acetylcholine induced contraction. Acetylcholine-induced contractions were abolished by indomethacin or endothelium rubbing. We conclude that endothelium-dependent relaxations are not diminished by spontaneous hypertension but the relaxations mediated by the muscarinic receptors are reduced with ageing. Further, acetylcholine causes endothelium-dependent contractions by releasing cyclo-oxygenase products, not only in SHR but also in aged normotensive WKY.

Experiments were conducted in conscious rats to determine whether DOCA-salt treatment could cause an elevation of sodium concentration of cerebrospinal fluid (CSF), which may be responsible for the enhanced activity of sympathetic nervous system (SNS) and increased secretion of vasopressin (AVP). Systolic blood pressure (SBP) and mean arterial pressure (MAP) were gradually but consistently increased by DOCA-salt treatment. Serum Na concentration was similarly increased with time by DOCA-salt, and significantly higher than control in the 4th treatment week. In contrast, DOCA-salt did not alter the CSF Na levels at any time during treatment. A relationship between SBP and CSF Na was never evident at any stage of the DOCA-salt hypertension. The decrese in MAP following admistratiom of the vasopressin V 1 -receptor antagonist, d(CH 2 ) 5 Tyr(Me)AAVP (30μg/kg), or hexamethonium (30mg/kg) was enhanced in the DOCA-treated rats, as compared to findings in the controls. These hypotensive effects were gradually, but progressively enhanced with the development of hypertension by DOCA-salt treatment. We tentatively conclude that mechanisms accounting for the enhanced activity of SNS and AVP in DOCA-salt hypertensive rats are independent of an increased Na concentration in the CSF.

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and in 72 with essential hypertension (EHT) to differentiate the two disorders during the following conditions on normal salt diet: after overnight recumbency (basal state) and 2 hours after oral administration of 25 mg of captopril. Screening criteria were determined so that all PA patients were diagnosed as positive, and their specificities were compared with those of other conventional screening methods for PA. After captopril administration, the specificity of a criterion based on a combination of PAC and PAC/PRA ratio was 93% and positive predictive value was 79%. This criterion was superior to blood pressure response to angiotension II analog infusion, PRA on salt depletion, and to PAC on salt loading. However, higher specificity (97%) and positive predictive value (90%) were obtained from a criterion based on a combination of basal PAC and PAC/PRA ratio. Therefore, the use of a combination criterion based on PAC and PAC/PRA ratio at basal state rather than after captopril administration may give a satisfactory result in the screening for PA.

We compared the glucose tolerance and insulin responses to intravenous (IV) glucose administration of a dose of 1 g/kg body weight in a conscious and unrestrained state of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) with catheters chronically indwelled into artery and vein. Both plasma glucose levels at two minutes and ten minutes following IV glucose load as well as the incremental and total areas of plasma glucose were slightly but significantly lower in SHR than in WKY. Glucose disappearance rate (K value) was 7.7 ± 0.3%/min in SHR, being slightly but significantly higher than that of 6.8 ± 0.3%/min in WKY. On the other hand, insulin responses to the glucose load at ten minutes and 30 minutes as well as incremental and total insulin areas were significantly lower in SHR than in WKY. There was no significant difference in insulinogenic index between SHR and WKY. Our observations suggest that in a conscious and unrestrained state, SHR have the greater glucose tolerance associated with reduced insulin secretion than do WKY.

The influence of a family history of hypertension on body mass index, serum lipids, uric acid, blood sugar and haematocrit was investigated in 579 young normotensives aged 19-35 years with or without a parental history of hypertension. Body mass index, total cholesterol, triglycerides and uric acid were significantly higher in offspring with a parental history of hypertension than in those without. There were no differences in blood sugar and haematocrit between the two groups. Multivariate analysis revealed that a parental history of hypertension influenced levels of body mass index, triglycerides and uric acid, independently of the level of blood pressure.

症例は53才の男性.立ちくらみと失神発作あり.血圧は臥位112/72,坐位72/60mmHg.体位変換試験で血圧は低下し,血中ノルエピネフリン濃度は不変,血中バゾプレッシン濃度は増加した.寒冷刺激で昇圧を認めず,ノルエピネフリン静注に過大反応を示した.錐体路・錐体外路症状はなく特発性起立性低血圧症と診断した. Fludrocortisoneとyohimbine 15mg/日の継続治療で,血圧は臥位150/100,坐位95/70mmHgに上昇し社会復帰した.

We examined the central action of NaCl on blood pressure using intracerebroventricular (i.c.v.) and intracisternal (i.c.) injections of hypertonic NaCl solution in conscious, unrestrained spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The dose-dependent pressor response produced by i.c.v. hypertonic NaCl was greater in SHR than in WKY rats, while the dose-related pressor action produced by i.c. NaCl did not differ between the two strains. The hyperresponsiveness to i.c.v. NaCl in SHR was abolished by pretreatment with an i.c.v. injection of the angiotensin II (ANG II) analogue 1-Sar, 8-IIeu ANG II. Both ANG II and a combination of ANG II and NaCl given by i.c.v. injection had a greater pressor response in SHR than in WKY rats, although both ANG II and phenylephrine given intravenously elevated blood pressure to the same extent in both strains. Furthermore, i.c.v. ANG II both with and without hypertonic NaCl caused dipsogenic behaviour which lasted longer in SHR than in WKY rats. This response to i.c.v. hypertonic NaCl without ANG II was not substantially different between the two strains. Intracisternal hypertonic NaCl did not induce drinking behaviour. These observations suggest that in the SHR, the third ventricle rather than the brain stem is a more sensitive area to NaCl. The brain renin-angiotensin system in the SHR may play an important role in this accelerated pressor response and may be responsible, at least to some extent, for the enhanced reaction to chronic oral salt loading.