EXAMINATION BY RADIOLIGAND BINDING OF THE ALPHA(1)-ADRENOCEPTORS IN THE MESENTERIC ARTERIAL VASCULATURE DURING THE DEVELOPMENT OF SALT-SENSITIVE HYPERTENSION

Previous experiments have suggested that the vascular smooth muscle of Dahl salt-sensitive (DS) rats may possess a difference in the alpha(1 )-adrenoceptor population or its transduction processes compared to Da hl salt-resistant (DR) rats. The purpose of the current research is to study the role of alpha(1)-adrenoceptors in the specific supersensiti vity to norepinephrine (NE) seen prior to and early in the development of hypertension in the DS rat. Experiments in isolated perfused super ior mesenteric arterial vasculature from DS rats chronically fed a hig h (7%) salt diet for 5 days or 3 weeks, in the absence or presence of an elevation in systolic blood pressure, respectively, demonstrated a specific supersensitivity to NE relative to DR rats. The enhanced resp onsiveness was specific to NE after 5 days of high salt since no diffe rences in sensitivity of these preparations was observed to either KCl or 5-HT. A small but significant elevation in sensitivity to KCl foll owing 3 weeks of treatment suggests that multiple factors may contribu te to tissue responsiveness at this time. Radioligand binding experime nts were performed using [I-125]-HEAT to study the alpha(1)-adrenocept or population and its subtypes. Saturation experiments using membranes prepared from the superior mesenteric arterial vasculature or mesente ric arterial branches showed no significant differences in overall alp ha(1)-adrenoceptor population between DS and DR rats fed a high-salt d iet for 5 days or 3 weeks. Competition experiments using membranes pre pared from the superior mesenteric arterial branches in the presence o f the alpha(1A)-subtype selective antagonist 5-methylurapidil showed t wo binding sites (high and low affinity) in these resistance vessels b ut no significant differences in nature or ratio of these sites betwee n the DS and DR groups. These results suggest that changes in the alph a(1)-adrenoceptor population are not responsible for the specific supe rsensitivity to NE, which may be an early event in the induction and d evelopment of hypertension.