SPECIFIC SUPERSENSITIVITY OF THE MESENTERIC VASCULAR BED OF DAHL SALT-SENSITIVE RATS

Dahl salt-sensitive (DS) and salt-resistant (DR) rats were maintained on a diet containing normal (0.45%) or high (7%) salt for 5 days. The DS rats had slightly higher systolic blood pressures than DR rats, although a high salt diet failed to significantly elevate pressure in either group when compared with their appropriate (low salt diet) controls. The sensitivity of the isolated, perfused mesenteric vasculature from DS rats fed a high salt diet to nerve stimulation was greater when compared with all other groups in the presence or absence of cocaine (1-mu-M). A similar difference in sensitivity between high salt DS rats and high salt DR rats to bolus injections of norepinephrine was observed only in the presence of cocaine. The change in sensitivity was characterized by a leftward shift of the dose-response curve without a change in maximum response. No difference in sensitivity between the high salt DS group and any other treatment group was observed in response to the pressor agents KCl, angiotensin II, 5-hydroxytryptamine or the depressor agent acetylcholine. These data indicate that DS rats on a short-term, high salt diet possess a significant and specific elevation in sensitivity to nerve stimulation and norepinephrine in the absence of an increase in blood pressure. Differences in the effectiveness of cocaine among the groups suggest that differences may exist in neuronal uptake (uptake 1). Although the greater neuronal uptake in preparations from high salt DS rats masks a greater sensitivity of the vascular smooth muscle to exogenous norepinephrine, supersensitivity of the smooth muscle may contribute to the enhanced responses to nerve stimulation since neuronal uptake has less influence on responses to neurally released norepinephrine. The specificity of the sensitivity difference suggests that the vascular smooth muscle of DS rats on high salt diets for 5 days possesses an abnormality either at the level of the alpha-1-adrenoceptor or in the sequelae that develop after adrenoceptor occupation. This could be an early event in the induction of hypertension in the Dahl rat.