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Objective: To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes.Research Design and Methods: Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (n = 18) after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55; women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA).Results: Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups.Conclusions: Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated. [ABSTRACT FROM AUTHOR]

A population-based study was performed in order to study the interrelationships of the circulating components of the renin-angiotensin system during basal conditions and their relations to blood pressure (BP), age and gender. One hundred and four women and 95 men, 18-70 years old, evenly age distributed and randomly selected from the population of Linköping, Sweden, participated. Venous blood was drawn at 08.00 hours and ambulatory BP recording was then performed. Serum angiotensin-converting enzyme (ACE) activity correlated with plasma angiotensin II (r = 0.20, P = 0.004), but when calculated separately according to gender, the correlation remained significant only in men (r = 0.33, P = 0,001). Plasma renin activity (PRA) correlated negatively with age (r = -0.30, P < 0.0001), but immunoreactive active renin (IRR) and angiotensin II did not. PRA and IRR correlated negatively with BP in women but correlations disappeared after age adjustment. The 23 women on oestrogen medication did not differ from the remaining 81 with respect to age (P = 0.6), IRR (P = 0.96) or angiotensin II (P = 0.4) levels, but PRA was higher (2.2 ± 1.4 ng Ang I/ml/h and 1.5 ± 0.9 ng Ang I/ml/h, respectively, P = 0.004). PRA (r = 0.38, P < 0.0001) and IRR (r = 0.49, P < 0.0001) correlated positively with the levels of angiotensin II. In conclusion the fact that PRA, but not IRR, declined with age and was higher among oestrogen-treated women, although angiotensin II was unaffected suggests IRR to be a more robust marker of angiotensin II levels than is PRA in a population-based setting. ACE correlates positively with angiotensin II in men. [ABSTRACT FROM AUTHOR]

Vasoactive humoral factors were measured in 27 patients before and during the first week of conventional treatment of acute heart failure. On admission, all patients were given frusemide intravenously, followed by oral digoxin and diuretic therapy. Before drug treatment, plasma renin activity and plasma angiotensin II concentrations were within normal ranges in the group of patients without previous diuretic treatment, but were significantly higher in those 16 patients already on diuretic drugs when admitted to hospital. After diuretic treatment, however, even the former group revealed activation of the renin-angiotensin system. Plasma concentrations of catecholamines were increased initially but normalized within 1 day. A majority of the patients initially had very high plasma concentrations of atrial natriuretic peptide (mean 276.9 ± 39.0 pg ml) which decreased but did not normalize during the study period. High plasma levels of arginine vasopressin (mean 56.8 ± 14.6 pg ml) were found, but tended to be reduced during treatment. Thus, patients with acute heart failure displayed increased plasma concentrations of atrial natriuretic peptide, arginine vasopressin and catecholamines, but these vasoactive hormones decreased in parallel to clinical improvement during diuretic therapy. In contrast, the renin-angiotensin system became clearly activated. [ABSTRACT FROM PUBLISHER]