Renal arteriolar Na+/Ca2+ exchange in salt-sensitive hypertension.

The present studies were performed to assess Na+/Ca2+ exchange activity in afferent and efferent arterioles from Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats. Renal arterioles were obtained by microdissection from S and R rats on either a low-salt (0.3% NaCl) or high-salt (8.0% NaCl) diet. On the high-salt diet, S rats become markedly hypertensive. Cytosolic calcium concentration ([Ca2+]i) was measured in fura 2-loaded arterioles bathed in a Ringer solution in which extracellular Na (Nae) was varied from 150 to 2 mM (Na was replaced with N-methyl-D-glucamine). Baseline [Ca2+]i was similar in afferent arterioles of R and S rats fed low- and high-salt diet. The change in [Ca2+]i (Delta[Ca2+]i) during reduction in Nae from 150 to 2 mM was 80 +/- 10 and 61 +/- 3 nM (not significant) in afferent arterioles from R rats fed the low- and high-salt diet, respectively. In afferent arterioles from S rats on a high-salt diet, Delta[Ca2+]i during reductions in Nae from 150 to 2 mM was attenuated (39 +/- 4 nM) relative to the Delta[Ca2+]i of 79 +/- 13 nM (P < 0.05) obtained in afferent arterioles from S rats on a low-salt diet. In efferent arterioles, baseline [Ca2+]i was similar in R and S rats fed low- and high-salt diets, and Delta[Ca2+]i in response to reduction in Nae was also not different in efferent arterioles from R and S rats fed low- or high-salt diets. Differences in regulation of the exchanger in afferent arterioles of S and R rats were assessed by determining the effects of protein kinase C (PKC) activation by phorbol 12-myristate 13-acetate (PMA, 100 nM) on Delta[Ca2+]i in response to reductions in Nae from 150 to 2 mM. PMA increased Delta[Ca2+]i in afferent arterioles from R rats but not from S rats. These results suggest that Na+/Ca2+ exchange activity is suppressed in afferent arterioles of S rats that are on a high-salt diet. In addition, there appears to be a defect in the PKC-Na+/Ca2+ exchange pathway that might contribute to altered [Ca2+]i regulation in this important renal vascular segment in salt-sensitive hypertension.