An INVESTIGATION INTO THE TYPE OF Β‐ADRENOCEPTOR MEDIATING SYMPATHETICALLY ACTIVATED RENIN RELEASE IN THE CAT

Abstract

1 Stimulation of the renal nerves in the cat was previously shown to cause renin release which could be blocked by propranolol. An attempt was made in this study to determine the type -ofadrenoceptor mediating this response. 2 In anaesthetized, unilaterally nephrectomized cats, a comparison was made of the ability of two selective 3-adrenoceptor antagonists to block the tachycardia and hypotension caused by isoprenaline (mediated respectively by 3l-and P2-adrenoceptors) and the release of renin caused by renal nerve stimulation. 3 Isoprenaline (mean dose of 0.224 ± 0.022 nmol/kg), increased heart rate by approximately 43 beats/min and decreased mean blood pressure by 47 mmHg. Stimulation of the distal cut ends of the renal nerves, at a rate sufficient to reduce renal blood flow by 30%, resulted in an approximately 150% increase in plasma renin activity.4 Administration of the selective ,1-adrenoceptor antagonist, atenolol (0.38 to 11.28 pmol/kg), caused a dose-related inhibition of nerve stimulated renin release and of isoprenaline-induced tachycardia, with no diminution of the vasodepressor response to isoprenaline; in contrast, the selective 32-adrenoceptor antagonist, erythro-DL-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol (ICI 118, 551, 0.03 to 2.86 imol/kg), caused a dose-related inhibition of the isoprenaline-induced vasodepression without altering the increase in plasma renin activity caused by renal nerve stimulation. Only at the highest dose of ICI 118, 551 was there a reduction of isoprenaline-induced tachycardia, by about 40%. 5 The selective inhibition of neurally activated renin release by atenolol but not by ICI,118,551 is consistent with the suggestion that the 13-adrenoceptors mediating renin release resemble those in the heart more closely than those in peripheral blood vessels.

Effect of Converting Enzyme Inhibition on the Renal Haemodynamic Responses to Noradrenaline Infusion in the Rat

“…It is generally accepted that adrenergically induced renin release from the juxtaglomerular cells of the kidney is mediated via 13-adrenoceptors (Reid etal., 1978) and it is likely that such a mechanism was responsible for the increased PRA observed following noradrenaline in the present study. Although a reduction in renal blood flow can act as a stimulus to renin release (Davis & Freeman, 1976), under conditions of adrenergic vasoconstriction almost all the renin release can be blocked by specific 3-adrenoceptor antagonists (Johns & Singer, 1974;Johns, 1981) and therefore in the present study it is probable that the reduction in renal blood flow would not contribute to the observed increases in PRA.…”

The role of α‐adrenoceptors in the regulation of renal tubular sodium reabsorption and renin secretion in the rabbit

“…1982). The neurally induced increase in renin secretion involves activation of P-adrenoceptors which are now recognized as being located on the juxtaglomerular granular cells (Keeton & Campbell, 1980) and have been classified as ,1-adrenoceptors (Johns, 1981;Osborn et al, 1981). These adrenergically mediated renal functional responses have also been described following noradrenaline administration directly into the renal artery of dogs at low doses which did not change renal haemodynamics (Barger et al, 1959;Pearson & Williams, 1968;Winer et al, 1971;Gill & Casper, 1972).…”

Microsphere analysis of β2‐adrenergic control of resistance in different vascular areas after hemorrhage

“…Tentatively, this discrepancy might be related to the possibility that the dilator response during isoprenaline infusion might be counteracted by PIadrenoceptor-mediated (cf. Keeton & Campell 1980, Johns 1981) release of renin-angiotensin. The possible existence of both PIand &adrenergic vascular effects with opposing influences might also explain why non selective /3-blockade failed to reveal any major renal resistance effect during hemorrhage (Lundvall & Gustafsson 1981).…”

“…administration of the highly 'selective' (O'Donnell & Wanstall 1980, Bilski et al 1983) &blocking agent ICI 118,55 1 [erythro-dl-l-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol, Imperical Chemical Industries Ltd., England] in a dose of 80 pgxkg bwt-'. This dose of the blocker has been shown to cause effective vascular B2adrenoceptor blockade within few rnin after application (Gustafsson & Lundvall 1984) without interfering with the P1-adrenoceptors of the heart (Johns 1981, Smith et al 1983, Bilski et al 1983).…”