Effect of sympathetic stimulation and intrarenal alpha‐blockade on the secretion of renin by the human kidney

Abstract

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.

Acute renal effects of doxazosin in man.

“…Therefore, one may infer that al-adrenoceptors exert a tonic inhibitory effect on renin secretion at rest, but apparently this mechanism is of lesser importance during activation of the adrenergic system. Again, this contrasts to our previous results where we found that phentolamine significantly enhanced renin release, not only at rest but also during handgrip exercise (de Leeuw et al, 1985). Thus, further studies with more specific antagonists are necessary to elucidate whether a2-receptors are more important than alreceptors in this respect.…”

“…The increase in renal perfusion following doxazosin infusion points to a role of a,-adrenoceptors in the mediation of renal vasoconstriction. Although the relative importance of these receptors cannot be assessed from our study, previous experiments in our laboratory indicated that the effect on renal blood flow was quantitatively greater when the nonselective drug phentolamine was infused (de Leeuw et al, 1985). Thus, it may be that a2-adrenoceptors have an even greater impact than do al-adrenoceptors on the regulation of renal blood flow.…”

α‐Adrenergic regulation of human renal function

“…These studies are based on the direct infusion of drugs into the renal artery of hypertensive patients undergoing diagnostic arteriography to exclude a stenosis of the renal artery. In their initial study these authors demonstrated that intrarenal infusion of vehicle did not affect renal blood flow or renovascular resistance, while infusion of the a-adrenoceptor antagonist, phentolamine (6 pg/kg/min), enhanced renal blood flow from 320 * 16 to 400 f 38 mUmird100 g kidney weight and reduced renovascular resistance from 0.38 * 0.10 to 0.29 0.14 units (n = 5 , P c 0.05); intrarenal infusion of the a, -adrenoceptor antagonist, doxazosin ( 1 pg/ kg/min), however, caused only very small alterations which barely reached statistical significance in some (de Leeuw et al, 1986;de Leeuw and Birkenhager, 1988) but not other studies (de Leeuw et al, 1985). In other studies these authors compared the effects of intrarenal infusion of the vehicle, doxazosin, and the %-adrenoceptor antagonist, yohimbine (1-10 pg/kg/min); in these studies yohimbine infusion significantly enhanced renal blood flow and this enhancement was always greater than those achieved by the a, -adrenoceptor antagonist, doxazosin (de Leeuw and Birkenhager, 1988;de Leeuw et al, 1987).…”

Renal Effects of α‐Adrenoceptor Blockade During Furosemide Diuresis in Conscious Rats

“…Thus, changes in filtration fraction (GFR/renal plasma flow) are considered to affect proximal tubular Na reabsorption by changes in postglomerular capillary oncotic pressure. We did not measure renal blood flow in this study, but other studies have demonstrated a renovascular vasodilating effect of phentolamine after intrarenal administration (de Leeuw et al 1985). Assuming that phentolamine counteracted the furosemide-induced reduction in renal blood flow , the filtration fraction would tend to be lower during simultaneous furosemide and phentolamine infusion than during furosemide alone.…”

“…The tubular effects of angiotensin I1 on the distal nephron segment is unclarified, although some evidence suggest that angiotensin 11 increases tubular Na reabsorption at nephron sites beyond the proximal tubules (Olsen 1985;Hall et al 1990). Thus, a potentiated renin release by phentolamineinduced reduction in MAP, might accelerate angiotensin I1 formation and ADRN, during simultaneous intravenous furosemide and phentolamine infusion (Keeton & Campbell 1981;de Leeuw et al 1985).…”