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 (Na(e)) 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) (Δ[Ca2+](i)) during reduction in Na(e) 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, Δ[Ca2+](i) during reductions in Na(e) from 150 to 2 mM was attenuated (39 ± 4 nM) relative to the Δ[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 Δ[Ca2+](i) in response to reduction in Na(e) 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 Δ[Ca2+](i) in response to reductions in Na(e) from 150 to 2 mM. PMA increased Δ[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.