Renal arteriolar Na1/Ca21 exchange in salt-sensitive hypertension

Nelson, Lawrence D., M. Tino Unlap, James L. Lewis, and P. Darwin Bell. Renal arteriolar Na1/Ca21 exchange in salt-sensitive hypertension. Am. J. Physiol. 276 (Renal Physiol. 45): F567–F573, 1999.—The present studies were performed to assess Na1/Ca21 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 ([Ca]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-methylD-glucamine). Baseline [Ca]i was similar in afferent arterioles of R and S rats fed lowand high-salt diet. The change in [Ca]i (D[Ca]i) during reduction in Nae from 150 to 2 mM was 80 6 10 and 61 6 3 nM (not significant) in afferent arterioles from R rats fed the lowand high-salt diet, respectively. In afferent arterioles from S rats on a high-salt diet, D[Ca]i during reductions in Nae from 150 to 2 mM was attenuated (39 6 4 nM) relative to the D[Ca]i of 79 6 13 nM (P , 0.05) obtained in afferent arterioles from S rats on a low-salt diet. In efferent arterioles, baseline [Ca]i was similar in R and S rats fed lowand high-salt diets, and D[Ca]i in response to reduction in Nae was also not different in efferent arterioles from R and S rats fed lowor 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 D[Ca]i in response to reductions in Nae from 150 to 2 mM. PMA increased D[Ca]i in afferent arterioles from R rats but not from S rats. These results suggest that Na1/Ca21 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-Na1/Ca21 exchange pathway that might contribute to altered [Ca]i regulation in this important renal vascular segment in salt-sensitive hypertension.