Since it is not known for certain which alpha-adrenergic receptors mediate renal vasoconstriction in human essential hypertension, we infused either doxazosin (n = 7) or yohimbine (n = 7) into the renal arteries of hypertensive subjects immediately prior to diagnostic angiography. Both agents caused an increment in renal blood flow as assessed with the xenon-washout technique. Doxazosin increased renal flow from 342 +/- 36 to 360 +/- 55 ml/min per 100 g (0.05 less than p less than 0.10). Yohimbine enhanced flow from 380 +/- 41 to 485 +/- 63 ml/min per 100 g (p less than 0.01). The effect of yohimbine was significantly greater than that of doxazosin. In a control group (n = 7) receiving only saline, no changes in renal blood flow occurred. Doxazosin enhanced renin secretion in the kidney by 10 +/- 4% over levels in controls (0.05 less than p less than 0.10), whereas yohimbine increased renin release by 80 +/- 23% (p less than 0.01). The latter increase was apparently not due to alterations in flow alone, since the arteriovenous gradient for renin also widened. We conclude that in resting conditions, neurogenic vascular tone in the kidney depends mainly upon activation of alpha 2-adrenergic receptors. Moreover, these receptors exert a tonic inhibitory influence on renin release.

This study was initiated to explore the possible involvement of renal alpha-adrenoceptors in the regulation of active and inactive renin. In fifteen hypertensive patients who proved not to have vascular abnormalities on diagnostic renal arteriography, blood samples were collected simultaneously from the renal artery and vein before and during an intrarenal infusion of either saline (n = 5), or the alpha-1 blocker doxazosin (n = 5) or the non-selective alpha-1 blocker doxazosin (n = 5) or the non-selective alpha-blocker phentolamine (n = 5). Subsequently, responses of renal blood flow and renin secretion were assessed following 3 min of handgrip exercise. In none of the experiments secretion of inactive renin could be detected. Release of active renin increased from 580 (SEM 170) to 650 (SEM 220) microU min-1 (100 g)-1 during infusion of doxazosin (P less than 0.05) and from 760 (SEM 100) to 1000 (SEM 340) microU min-1 (100 g)-1 during infusion of phentolamine (P less than 0.01). Saline infusion had no effect on secretion of active renin. While handgrip exercise had no significant effect on active renin secretion in the saline and in the doxazosin group, it enhanced secretion from 1000 (SEM 340) to 1280 (SEM 390) microU min-1 (100 g)-1 in the phentolamine group (P less than 0.01). The results indicate that mainly alpha-2 adrenoceptors exert an inhibitory effect on release of active renin, although alpha-1 receptors participate to some degree. There is no evidence that the kidney secretes inactive renin.

To evaluate the role of alpha 1‐adrenoceptors in the regulation of renal blood flow and renin secretion, we infused doxazosin in incremental doses (group I, n = 5) or at a fixed rate of 1 microgram kg‐ 1 min‐1 (group II, n = 6) into the renal artery of hypertensive patients just prior to diagnostic renal angiography. In group I, stepwise increasing doses of doxazosin were associated with increases in renal perfusion and, at doses above 1 microgram kg‐1 min‐1, also with a fall in blood pressure. Compared with observations in control subjects, doxazosin enhanced renal renin release at rest but did not modify the renin response to isometric exercise in group II. alpha 1‐ Adrenoceptors are involved in causing renal vasoconstriction and inhibition of renin secretion. However, the latter is only of importance in resting subjects.

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ABS TRACTIn 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 45O 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. 2285