Reduced renal vascular response to nerve stimulation and norepinephrine in DOCA–salt hypertensive rats

Abstract

Vascular responses to nerve stimulation and norepinephrine (NE) administration were studied in kidneys perfused in situ at constant flow in uninephrectomized Sprague–Dawley rats made hypertensive by 5–6 weeks of deoxycorticosterone acetate (DOCA) – salt treatment. One- and two-kidney normotensive rats were used as controls. Renal blood flow on a weight basis did not differ significantly between the two control groups. Kidneys of DOCA–salt rats were nearly twice the size of those in one-kidney controls, but blood flow was only half that of controls when perfusion pressure was set at 100 mmHg (1 mmHg = 133.322 Pa). There were no differences in renal vascular responses to nerve stimulation (2–8 Hz) or NE (10–50 ng, ia) between the two control groups; however, in the DOCA–salt rats, responses to nerve stimulation were decreased by 71–87%, while those to NE were decreased by 35–40%. Similar reductions in the response to barium chloride were seen. NE concentration in the perfused kidneys averaged 183 ± 11, 104 ± 16, and 37 ± 3 ng/g in the two-kidney, one-kidney, and DOCA–salt groups, respectively. The decrease in NE concentration in DOCA–salt kidneys was greater than could be accounted for by changes in renal mass alone. In another group of uninephrectomized rats, renal vascular resistance was increased to levels seen in DOCA–salt kidneys by iv infusion of NE. Under these conditions, responses to bolus injections of NE (50 ng) were decreased by 38%. Taken together, the results suggest that renal vascular responses to nerve stimulation in DOCA–salt kidneys are markedly reduced because of (i) a reduced amount of NE available for release, and (ii) a decreased responsiveness of the renal vasculature to NE. The latter response, which may extend to other vasoconstrictors as well, is opposite to what has been shown frequently in isolated, perfused kidneys, and may be explained by the presence of elevated renal vascular tone in DOCA–salt kidneys perfused in situ.