Efficacy of ramipril versus enalapril in patients with mild to moderate essential hypertension.

This double-blind, randomised, cross-over study investigated the antihypertensive efficacy of ramipril and enalapril was completed by 30 patients with mild-to-moderate essential hypertension. After a four-week placebo run-in phase, the patients received either 2.5mg ramipril or 10mg enalapril once daily for four weeks. The dosages were increased to 5mg ramipril and 20mg enalapril for a further four weeks. After a placebo washout phase of four weeks, the patients were crossed over to the alternative treatment. The decrease in average 24-hour ambulatory diastolic blood pressure from week 0 to week 8 was 1.6mmHg greater with ramipril than enalapril (90% confidence interval 0.6-2.7mmHg). The corresponding reduction in for systolic blood pressure was also greater with ramipril than enalapril by 2.4mmHg (90% confidence interval: 0.5-4.2mmHg). For the difference in the drop of 24-hour ambulatory diastolic blood pressure between ramipril and enalapril the lower level of the 90% confidence interval (CI) is above the clinically relevant difference of -3mmHg. This is an indication that ramipril (2.5 and 5mg dose) is at least as effective as enalapril (10 and 20mg dose) in decreasing blood pressure in patients with mild-to-moderate essential hypertension. The duration of adequate antihypertensive effect was relatively long for both ramipril and enalapril; however, ramipril tended to have a more prolonged antihypertensive effect. Ramipril had a higher diastolic and systolic trough/peak ratio than enalapril, resulting in a more uniform antihypertensive effect over the 24-hour treatment period. Both ramipril and enalapril were well tolerated and the two treatment groups had similar safety profiles.

Control of plasma arginine vasotocin in Kelp gulls (Larus dominicanus): roles of osmolality, volume, and plasma angiotensin II.

The physiological roles of plasma osmolality, volume, and angiotensin II (AII) in the control of plasma arginine vasotocin (AVT) have been evaluated in the Kelp gull. Plasma AVT (measured by radioimmunoassay) consistently followed the changes in plasma osmolality induced by dehydration, intravenous (iv) infusion of hypertonic saline, or iv infusion of hypotonic glucose solution. Osmoreceptor control of AVT was further characterized by the stimulatory effect of iv hypertonic mannitol but lack of effect of iv hypertonic urea. A direct volume effect on AVT release was demonstrated during hemorrhage, but blood volume reductions in excess of 10% were required. However, the volume of the extracellular fluid (ECF) compartment does have an important role in modulating the osmotic release of AVT in a way that enables contraction or expansion of ECF to be more expeditiously corrected than would occur if osmoreceptors alone regulated plasma AVT. Any physiological role of plasma AII in the control of plasma AVT is doubtful because after the iv infusion of AII for 60 min at 10, 25, 50, and 100 ng.min-1, only the two highest doses of AII, which produced supraphysiological plasma AII levels, caused elevations of plasma AVT. In addition, the osmotic reactivity of AVT release was not altered by exogenous administration of AII.

Control of renal and extrarenal salt and water excretion by plasma angiotensin II in the kelp gull (Larus dominicanus).

The osmoregulatory effects of intravenously (i.v.) administered angiotensin II (AII) at dose rates of 5, 15 and 45 ng.kg-1.min-1 were examined in kelp gulls utilizing salt gland and/or kidneys as excretory organs. In birds given i.v. infusion of 1200 mOsmolal NaCl at 0.3 ml.min-1 and utilizing only the salt glands to excrete the load, infusion of AII for 30 min consistently inhibited salt gland function in a dose-dependent manner. In birds given i.v. infusion of 500 mOsmolal NaCl at 0.72 ml.min-1 and utilizing both salt glands and kidneys to excrete the load, each dose of AII given for 2 h inhibited salt gland function but stimulated the kidney, so that the overall outputs of salt and water were enhanced and showed significant (2P less than 0.01) positive correlations with plasma AII. In birds given i.v. infusion of 200 mOsmolal glucose at 0.5 ml.min-1 and utilizing only the kidneys to excrete the load, low doses of AII (5 and 15 ng.kg-1.min-1) caused renal salt and water retention, whereas a high dose (45 ng.kg-1.min-1) stimulated salt and water output. The actions of plasma AII in kelp gulls support the concept that this hormone plays a vital role in avian osmoregulation, having effects on both salt gland and kidney function. Elevation of plasma AII consistently inhibits actively secreting salt glands, but its effects upon renal excretion depend primarily on the osmotic status as well as on the plasma AII concentration. In conditions of salt and volume loading doses of AII stimulate sodium and water excretion. With salt and volume depletion, the action of AII is bi-phasic with low doses promoting renal sodium and water retention but high circulating levels causing natriuresis and diuresis.

Plasma arginine vasotocin and angiotensin II in the water deprived Kelp gull (Larus dominicanus), Cape gannet (Sula capensis) and Jackass penguin (Spheniscus demersus).

1. The basal levels of the osmoregulatory hormones, arginine vasotocin (AVT) and angiotensin II (AII) were measured (by radioimmunoassay) in the plasma of conscious Kelp gulls, Cape gannets and Jackass penguins. 2. The responses of the hormones to similar degrees of hypertonicity and hypovolemia caused by water deprivation have also been determined. 3. Dehydration elevated plasma AVT and plasma AII in all three species. 4. The AVT concentration was increased by 2-4 fold and although in each case the correlation between plasma osmolality and plasma AVT was highly significant (2P less than 0.01), the sensitivity of release was greater in the gull (1.13 pg/ml per mOsm/kg) than in the gannet (0.36 pg/ml per mOsm/kg) or penguin (0.44 pg/ml per mOsm/kg). 5. Dehydration increased plasma AII 3-fold in the three bird types.