Stimulation of renin by blockade of alpha 2-adrenoceptors in man: role of the beta 1-adrenoceptor.

Previous experiments have shown that blockade of intrarenal alpha 2-adrenoceptors will cause a rise in renin secretion. Therefore, we designed the present study to explore whether this could be due to noradrenaline being released by a prejunctional mechanism and stimulating post-junctional beta 1-adrenoceptors. Two groups of patients in whom diagnostic renal angiography was indicated were studied before administration of contrast material. None of the patients had taken any antihypertensive medication in the 3 weeks preceding this investigation. In group I (n = 8) glucose was infused into the renal artery for 20 min; during the last 10 min yohimbine was also infused at a rate of 3 micrograms/kg per min. In group II (n = 8) the same protocol was carried out with the exception that, instead of glucose, we infused atenolol in a dose of 1 micrograms/kg per min. Blood samples for noradrenaline and renin were taken before infusions started, following 10 min of the glucose (or atenolol) and at the end of the yohimbine infusion. At the same time blood pressure and renal blood flow (133Xe-washout) were measured. The results show that yohimbine increased renin release by 310 +/- 60% in group I, but by only 80 +/- 45% in group II (P less than 0.01). However, noradrenaline 'release' was stimulated to the same degree in both groups (150 +/- 80 versus 138 +/- 75%; NS) During the experiments blood pressure and heart rate did not change. The data are consistent with the hypothesis that the effect of alpha 2-adrenoceptors on renin release is mediated by beta-adrenoceptors. Thus, the relevant alpha 2-receptor may be located prejunctionally.

[Effect of calcium inhibitors on sympathetic activity]. / Effet des inhibiteurs calciques sur l'activité sympathique.

Interference with the function of the sympathetic nervous system is one of the possible mechanisms whereby calcium-antagonists may lower blood pressure. We have studied the effects of one of those drugs (verapamil) on blood pressure and basal levels of catecholamines. The hypotensive response appeared to be associated with a small insignificant rise in noradrenaline and a significant fall in adrenaline. To explore the role of extracellular calcium we infused calcium gluconate before and during treatment with verapamil. Calcium had only little effect on plasma noradrenaline, but markedly stimulated adrenaline. The latter was not affected by verapamil when given intravenously, but clearly blunted after a period of oral treatment with verapamil. Noradrenaline release was enhanced by calcium during administration of verapamil. It is concluded that extracellular calcium may be involved in the secretion of adrenaline and that this requires transmembrane calcium influx. Perhaps a reduction in circulating adrenaline contributes to the blood pressure lowering effects of verapamil.

Humoral changes during and following coronary bypass surgery: relationship to postoperative blood pressure.

In this study we investigated the role of the renin-angiotensin system and the adrenergic system in the hypertensive response during and following coronary bypass surgery. Arterial blood samples for measurement of active renin, angiotensin II, aldosterone and catecholamines were drawn before, during and in the first period after coronary artery grafting. Both noradrenaline and adrenaline rose significantly during extracorporeal circulation and remained elevated afterwards, the rise in adrenaline preceding that of noradrenaline. During cardiopulmonary bypass renin also increased while angiotensin II increased after an initial fall. Postoperatively, renin tended to return to control levels. However, angiotensin II fell in some patients but remained elevated in others. The latter group had significantly lower blood pressure during cardiopulmonary bypass, but higher pressure thereafter. Aldosterone levels were markedly reduced during cardiopulmonary bypass. The results suggest that low pressure during extracorporeal circulation may trigger enhanced formation of angiotensin II, apparently involving extrapulmonary converting enzyme. This mechanism may, when acting in concert with an activated sympathetic nervous system, produce significant blood pressure elevation postoperatively.

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.