Role of Alpha-2 Receptors in the Regulation of Renal Function

Postsynaptic binding sites for alpha 1 and alpha 2 adrenoceptor ligands are found in abundance in the renal cortex of several species, with reports of 2-3 times as many alpha 2 as alpha 1 sites. These alpha adrenoceptor subtypes can potentially influence salt and water excretion through both vascular and tubular effects. Renal vascular resistance in dogs is increased by both alpha adrenoceptor subtype agonists but alpha 1 agonists are more potent. In rats, alpha 2, agonists have almost no effect on the renal circulation whereas alpha 1 agonists are capable of intense renal vasoconstriction. The mechanisms by which alpha 2 agonists increase glomerular filtration rate are not yet clear and may involve the secondary release of hormones affecting glomerular dynamics and permeability. Thus, an abundance of alpha 2 adrenoceptor binding sites in whole cortical homogenate of rat kidneys with little demonstrable vascular effect of alpha 2 agonist suggests that the preponderance of these receptors lies instead on the tubular epithelium. Alpha-1 adrenoceptors are probably responsible for the increased Na reabsorption from the proximal tubule and the anti-natriuresis following low level renal nerve stimulation. In contrast, an alpha 2 agonist such as guanabenz produces a diuresis by reducing the release of vasopressin and by antagonizing its hydrosmotic effect on the nephron, and a modest natriuresis by decreasing medullary interstitial osmolality and reducing passive Na reabsorption.