Physiological effects of short-term treatment with enalapril in hypertensive patients.

To assess the effects of enalapril eight hospitalized hypertensive patients on constant sodium intake were treated with incremental doses of this angiotensin converting enzyme blocking drug. After four days of placebo treatment enalapril was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the 1.25 mg dose, angiotensin II (AII) and blood pressure did not change significantly, despite a 50% reduction in converting enzyme activity. There were, however, significant increases in noradrenaline, renin and aldosterone. With high doses a more pronounced reduction in converting enzyme activity was found while AII, aldosterone and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension did not occur. With continued treatment renal vascular resistance decreased concurrently with enhanced natriuresis and a reduction in body weight. Plasma volume rose slightly. The data indicate that enalapril may lower blood pressure by converting enzyme inhibition, but sodium loss and a decrease in sympathetic activity are associated features.

Humoral and renal effects of MK-421 (enalapril) in hypertensive subjects.

To assess the effect of MK-421 (enalapril) we treated six hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin-converting enzyme blocking drug. After a few days of placebo treatment, MK-421 was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the lowest dose, converting enzyme activity was reduced by 50%, but angiotensin II and blood pressure did not change significantly. There were, however, significant increases in noradrenaline, renin, and aldosterone. With higher doses there was a more pronounced reduction in converting enzyme activity, while angiotensin II, aldosterone, and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension was not observed. With continued treatment, renal vasodilatation and enhanced natriuresis occurred together with a 1.2 kg decrement in body weight. Concurrently plasma volume rose, but renal blood flow remained unchanged. The data indicate that MK-421 effectively lowers blood pressure, and it does so by converting enzyme inhibition; sodium loss and a decrease in sympathetic activity are associated features. Since plasma volume increased despite enhanced natriuresis, the drug may act both at the arteriolar and at the venular level.

Aldosterone response to antihypertensive treatment.

To investigate whether changes in aldosterone during antihypertensive treatment would be related to alterations in the renin-angiotensin system or to changes in sodium-fluid balance, 54 essential hypertensives were hospitalized. Sodium intake was restricted to 55 mmoles per day. Levels of renin, angiotensin II and aldosterone were measured before and after two weeks treatment with atenolol (n=15), prazosin (n=15), the converting enzyme inhibitor MK 421 (n=6), verapamil (n=9) and the vasodilator L 6150 (n=10). Daily sodium excretion was determined from 24 h urine collections. The results indicate that, when renin or angiotensin levels do not change, the aldosterone response depends on alterations in sodium balance. When the renin system is depressed, sodium loss may prevent a large drop in aldosterone levels. It is concluded that during antihypertensive treatment body sodium status in itself modifies aldosterone secretion, irrespective of the renin-angiotensin system.

Effect of sympathetic stimulation on inactive renin.

In the present study we investigated the effect of three manoeuvres known to be associated with enhanced sympathetic activity on plasma levels of active and inactive renin. To this end, active and trypsin-activatable renin were measured in blood drawn from 12 untreated essential hypertensive patients before, during and after any of the following tests: isometric exercise (handgrip), noise stimulation and 45 degrees head-up tilt. These studies were repeated after the patients had been treated with either atenolol (n = 6) or SL 77499 (n = 6), an alpha-1 adrenoceptor blocking agent for 10 days. The results indicate that active and inactive renin often change in an unpredictable way in response to sympathetic stimulation. There are, as yet, no conclusive explanations which describe the behaviour of both forms of renin during these manoeuvres.

Neurohumoral response to hospitalization in hypertensive patients.

1. To investigate whether reduced activity of pressor systems could explain the spontaneous drop in pressure upon hospitalization, 51 subjects with uncomplicated essential hypertension were admitted to hospital. Sodium intake was fixed at 55 mmol/day. 2. Blood samples for noradrenaline, adrenaline, active renin, angiotensin II and aldosterone were drawn on each morning of the first 3 days of hospitalization; blood pressure was measured at 2 h intervals and values were averaged for each day. 3. Subjects were divided in two groups depending on whether they became normotensive (group 1; n = 12) or remained hypertensive (group 2; n = 39). This distinction was thought to reflect mild and more severe hypertensive groups respectively. 4. Although both groups showed a comparable fall in blood pressure during hospitalization, noradrenaline levels fell more consistently in group 1, whereas adrenaline levels fell only in group 2. The components of the renin--angiotensin--aldosterone system rose, but more conspicuously in group 1. 5. It is concluded that withdrawal of sympathetic activity can only partly explain the hypotensive response to hospitalization. The renin--angiotensin system behaves only passively and appears to be counterproductive to alterations in blood pressure.

Renin secretion by the human kidney.

1. 20 subjects with uncomplicated essential hypertension were studied, 10 of whom were on propranolol treatment. Several blood samples for determination of total and active renin were drawn simultaneously from the renal artery and vein after angiographic studies. 2. In all patients renal blood flow was measured by Hippuran-clearance at the time of blood sampling. Intrarenal blood flow was assessed by xenon-washout. 3. The results indicate that under basal conditions renin is secreted mainly in the active form, although secretion of inactive renin does occur. During propranolol treatment there is a tendency for secretion of active renin to be reduced.