Role of alpha 1- and alpha 2-adrenergic receptors in the human hypertensive kidney.

Abstract

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.

Renal alpha 2-adrenergic receptors and hypertension.

“…For example, in contrast to the results of DiBona and Sawin, 8 de Leeuw et al 17 recently observed a marked increase in renal blood flow and renin release with the infusion of yohimbine into the renal artery of conscious patients with essential hypertension. In these preliminary studies, yohimbine was much more effective than prazosin, suggesting a predominant role for the a 2 -adrenergic receptor in the control of renal vascular resistance in patients with essential hypertension.…”

The Renal Microcirculation

“…It is noteworthy that renal denervation in the rabbit increases RBF, indicating a tonic renal vasoconstrictor action of RSNA [1684] . However, other studies show that stimulation of α 2-adrenoceptors can also produce a weak renal vasoconstriction in experimental models [1688][1689][1690][1691][1692] and humans [1693] . Low intensities of nerve activity ( Ͻ 1 Hz) stimulate renin release via release of NE acting on β 1 -adrenoceptors on JG cells.…”

Interaction between alpha 2-adrenergic and angiotensin II systems in the control of glomerular hemodynamics as assessed by renal micropuncture in the rat.

“…Although the physiological role of renal a2 adrenoceptors remains to be fully established, they have been reported to constrict (11)(12)(13) or relax (2) the renal vasculature, suppress renin secretion (14,15), and stimulate reabsorption ofsodium from the proximal nephron by stimulating Na/H exchange (16)(17)(18) and from the loop ofHenle by suppressing furosemide- (19) or prostaglandin-(20) mediated increases in cAMP. a2 Receptors also inhibit reabsorption of salt and water from the distal nephron by antagonizing the effects of vasopressin (21)(22)(23)(24)(25) and potentiating the effect ofatrial natriuretic peptide (26).…”

“…In fact, administration of B-HT 933 to euvolemic rats with intact renal nerves resulted in an actual increase in nephron plasma flow despite a decline in blood pressure (2), probably because ofsuppression of efferent renal sympathetic nerve activity by central (30) or peripheral presynaptic a2 receptors (29,30,43,44). a2-Mediated renal vasoconstriction has been demonstrated, however, in awake rats ( 13,45 ), sheep ( I1), and humans ( 12), suggesting the possibility of a saturable vasomotor response that is obscured by the increase in circulating catecholamines accompanying general anesthesia (46). The present study confirms the previous finding, that a2 agonist administration does not alter nephron plasma flow in the euvolemic anesthetized rat after renal denervation (2).…”