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

Abstract

1 A study was undertaken in the anaesthetized rabbit to classify the a-adrenoceptor subtypes responsible for increasing renal tubular sodium reabsorption and renin secretion. Intrarenal administration of noradrenaline, at doses which did not change renal blood flow or glomerular filtration rate, significantly decreased urine flow, absolute and fractional sodium excretion by between 26% and 29%. These renal responses to noradrenaline were abolished by the selective a,-adrenoceptor antagonist, prazosin, but not by the selective M2-adrenoceptor antagonist, idazoxan. 2 Noradrenaline, given intrarenally, increased renin secretion between two and three fold and this response was not modified by either prazosin or idazoxan. 3 Intrarenal administration of the selective a-adrenoceptor agonists, phenylephrine and methoxamine, at dose rates which did not change renal haemodynamics, significantly reduced urine flow, absolute and fractional sodium excretion by 15% to 33%, but at doses which reduced blood flow and filtration rate, by between 11% and 26%, urine flow, absolute and fractional sodium excretion decreased between 42% and 49%. 4 Infusion of guanabenz (selective M2-adrenoceptor agonist), at doses with no renal haemodynamic action, increased urine flow, absolute and fractional sodium excretion by 11 % to 15%, while at doses which decreased blood flow by 7%, these other variables did not change. 5 Administration of UK 14304 (selective o2-adrenoceptor agonist) reduced blood flow and filtration rate by 3% and 9% respectively but had no other measurable action. At higher doses, which decreased blood flow by 14% and filtration rate by 24%, urine flow, absolute and fractional sodium excretion fell by between 27% and 50%. 6 Renin secretion was significantly increased by the high doses of phenylephrine and UK 14304 but not by the low doses of these drugs. 7 These studies show that adrenergic stimulation of renal tubular sodium reabsorption involves the activation of al-but not M2-adrenoceptors. Further, adrenergic activation of the juxtaglomerular cells to release renin does not appear to involve either al-or M2-adrenoceptors.

Alpha 2 adrenergic agonists stimulate Na+-H+ antiport activity in the rabbit renal proximal tubule.

“…Both data obtained in whole animal experiments or performed on the isolated perfused kidney tend to support this view (1)(2)(3)(4). The enhanced rate of catecholamine-induced solute flux across the tubular epithelial cell is attributed primarily to alpha adrenergic agonist activity.…”

α1b‐Adrenoceptors mediate renal tubular sodium and water reabsorption in the rat

“…Furthermore, SZL-49 (Elhawary et al, 1992) and the Ca2l entry blocker, nifedipine (Han et al, 1990) (Osborn & Harland, 1988), stimulation of gluconeogenesis (Kessar & Saggerson, 1980) and, increased renovascular resistance (Cooper & Malik, 1985;Wolff et al, 1987;DiBona & Sawin, 1987;Jeffries et al, u) 1987). Intrarenal arterial infusion of PE in anaesethetized rabbits, at a dose which did not alter renal haemodynamics, significantly reduced urine flow and absolute and fractional * Nat excretion by about 15, 23, and 23% respectively (Hesse & Johns, 1985). Higher doses of PE, which caused 11% decrease of blood flow and 15% decrease in filtration rate, 0-A i were found to decrease urine flow, absolute and fractional Na' excretion by 43%, 49% and 42% respectively.…”

A study in the rat of the renal actions of nitrendipine and diltiazem on the adrenergic regulation of calcium and sodium reabsorption

“…However, there is evidence that at vascular smooth musclejunctions, foi example rat aorta and rabbit coronary artery (Vanhoutte & Rimele, 1982), and in spontaneously hypertensive rat models (Kazda et al, 1985), that a1-adren-oceptor-mediated vasoconstrictor responses can be dependent on inward movement of calcium. Renal nerve-induced increases in tubular sodium reabsorption appear to be mediated by oxi-adrenoceptors in the dog (Osborn et al, 1983), the rabbit (Hesse & Johns, 1985) as well as the rat (Johns & Manitius, 1986b) and the possibility existed that calcium channel blockers could interfere with neurotransmission at this specialized junction. However, the magnitude of the reduction in the calcium excretion due to the low frequency renal nerve stimulation was not altered by either dose of drug.…”

“…It is now recognized that activity within these nerves can directly stimulate the reabsorption of sodium ions by the tubular epithelial cells and in a recent study (Johns & Manitius, 1986a) calcium reabsorption was shown to be similarly regulated. The action of the sympathetic nerves on the epithelial cells involves aadrenoceptors (Hesse & Johns, 1985) and the possibility arises that the calcium channel blocking drugs, which have the functional properties of (x-adrenoceptor antagonists, could decrease the effectiveness of the renal nerves.…”