Renal alpha-adrenoceptor density and blood pressure in SHR rats exposed chronically to prazosin and/or yohimbine.

In the present study we evaluated the effect of selective alpha 1 and alpha 2-adrenoceptors blockade on the development of hypertension and on renal alpha-adrenoceptor densities in the spontaneously hypertensive rats (SHR). In these rats, daily intraperitoneal administration of 0.1 mg/kg of prazosin, yohimbine or prazosin + yohimbine for seven weeks significantly retarded the development of hypertension. In an attempt to characterize the relationship between changes in blood pressure and the renal alpha-adrenoceptor number after a prolonged alpha-blockade in the SHR, we have used 3H-prazosin and 3H-yohimbine as the selective ligands for alpha 1 and alpha 2-adrenoceptors. Saturation studies showed that renal alpha 1 and alpha 2-receptor densities were significantly decreased by prazosin and yohimbine, respectively, in SHR. Equilibrium dissociation constants (KD), however, were similar for both classes of receptors in experimental and control rats. In WKY rats, to the contrary, only prolonged administration of yohimbine and prazosin + yohimbine for seven weeks decreased the number of 3H-binding sites, and this decrease consisted in a Bmax change rather than an affinity (KD) change. Thus, the study provides evidence that the elevated blood pressure in the SHR is related, at least in part, to an abnormality in the adrenergic system control.