Cellular mechanisms in vascular smooth muscle contributing to the development of salt-sensitive hypertension.

The purpose of this research is to study the cellular mechanisms responsible for the specific supersensitivity to norepinephrine seen in the superior mesenteric vasculature of Dahl salt-sensitive (DS) rats prior to and early in the development of hypertension. It is hypothesized that the vascular smooth muscle of DS rats on a high salt diet for five days or three weeks possess an abnormality at the level of the {dollar}\\alpha\\sb1{dollar}-adrenoceptor or in the transduction process activated after adrenoceptor occupation. The vasoconstrictor response to various agonists was studied in isolated perfused superior mesenteric arterial vasculature from DS rats fed a high salt diet for five days or three weeks to determine if the arterial vasculature demonstrates a specific supersensitivity to norepinephrine compared to Dahl salt-resistant (DR) rats. The functional distribution and role of the {dollar}\\alpha\\sb1{dollar}-adrenoceptor subtypes in the vasoconstrictor response was studied in the arterial vasculature from these animals. Finally, radioligand binding methods were used to examine the {dollar}\\alpha\\sb1{dollar}-adrenoceptor population and its subtypes. The results showed that the superior mesenteric arterial vasculature from DS rats fed a high salt diet for five days or three weeks, in the absence or presence of an elevation in systolic blood pressure, respectively, showed a specific supersensitivity to norepinephrine compared to DR rats. In the presence of the al-subtype selective antagonists 5-methylurapidil (5-MU) or CEC, the DS high salt group showed significantly different responses to norepinephrine in some aspects compared to DR rats. Saturation experiments using membranes prepared from the superior mesenteric arterial vasculature or arterial branches showed no significant differences in overall {dollar}\\alpha\\sb1{dollar}-adrenoceptor population between DS and DR rats fed a high salt diet for five days or three weeks. Competition experiments using membranes prepared from the arterial branches in the presence of the {dollar}\\rm\\alpha\\sb{lcub}1A{rcub}{dollar}-subtype selective antagonist 5-MU showed two binding sites in these resistance vessels but no significant differences in these sites between the DS and DR groups. It is concluded that changes in the {dollar}\\alpha\\sb1{dollar}-adrenoceptor population are not responsible for the specific supersensitivity to norepinephrine seen prior to and early in the development of salt-sensitive hypertension