Alterations in Cardiac Alpha and Beta Adrenoceptors During the Development of Spontaneous Hypertension

To study potential cardiac receptor alterations during the development of spontaneous hypertension, specific binding of [3H]-2-N(2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane, (-)-[3H]dihydroalprenolol and (-)-[3H]quinuclidinyl benzilate in ventricles of Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) at different ages was determined. The Kd and maximal binding for specific binding of [3H]-2-N(2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane and (-)-[3H]dihydroalprenolol in ventricular homogenates of SHR and SHRSP at prehypertensive ages were similar to those of age-matched WKY. With the development of spontaneous hypertension in SHR and SHRSP, there was a significant decrease in the maximal binding for both ligands without a change in Kd. The decrease in maximal binding in SHR and SHRSP at 10 weeks of age was 29 to 38%, compared with age-matched WKY. There was no difference in ventricular (-)-[3H]quinuclidinyl benzilate binding between WKY and SHRSP. Hofstee analysis of the inhibition of ventricular (-)-[3H]dihydroalprenolol binding by practolol demonstrated a specific 51% decrease in ventricular beta-1 receptor density in 10-week-old SHRSP. In addition, the inotropic response to isoproterenol in isolated papillary muscles from SHRSP was significantly smaller than that in WKY. Thus, it is concluded that during the development of spontaneous hypertension in SHR and SHRSP, there is a specific loss in number of cardiac alpha and beta-1 adrenoceptors with a consequently reduced responsiveness of isolated papillary muscles to isoproterenol in SHRSP. These results are compatible with the reported increase in sympathetic outflow to the cardiovascular system in spontaneous hypertension.