We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall.(ABSTRACT TRUNCATED AT 250 WORDS)

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Uraemic autonomic dysfunction is reckoned to participate in dialysis hypotension, but a clear relationship has not been established. However, autonomic function is usually tested at rest, and possibly autonomic dysfunction arises or worsens during dialysis. We therefore performed easily repeatable tests of efferent sympathetic function, that is static exercise test and parasympathetic function, that is heart rate variability during Valsalva manoeuvre and deep breathing, at successive stages of a standard haemodialysis session; before dialysis, 20 min after dialysis without ultrafiltration, after 3 h of dialysis combined with ultrafiltration, and 20 min after dialysis. Studies were performed in 22 patients on chronic haemodialysis on a cuprophane dialyser. The mean ultrafiltration volume was 2.2 +/- 0.61. We found that blood pressure elevation upon static exercise, and heart rate variability during Valsalva or deep breathing test remained unaltered at the various stages of dialysis. On past performance the patients were divided into hypotension prone (n = 6) or resistant (n = 16). Hypotension prone patients showed a greater blood pressure drop during dialysis, but also showed an appropriately enhanced heart rate acceleration. The occurrence of autonomic dysfunction was not elevated in this group, nor did such dysfunction develop along dialysis. Predialysis parasympathetic function tests were abnormal in 10 patients. These patients also showed an augmented intradialytic blood pressure decrease, but no enhanced acceleration in heart rate. Their parasympathetic dysfunction did not worsen during dialysis. Based upon the predialysis exercise test, low responding patients (blood pressure increase 5 +/- 2 mmHg, n = 11) were distinguished. These subjects were not characterized by a greater blood pressure decrease or different heart rate acceleration. Generally, the responses upon exercise, whether low or high, remained unaltered during dialysis. we conclude that haemodialysis has no systematic effect on autonomic function. Hypotension-prone patients are not distinguished by a disturbed predialytic or intradialytic autonomic blood pressure control.

Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability.