Contribution of cytochrome P-450 v-hydroxylase to altered arteriolar reactivity with high-salt diet and hypertension

Frisbee, Jefferson C., John R. Falck, and Julian H. Lombard. Contribution of cytochrome P-450 v-hydroxylase to altered arteriolar reactivity with high-salt diet and hypertension. Am J Physiol Heart Circ Physiol 278: H1517–H1526, 2000.—The present study evaluated the contribution of cytochrome P-450 v-hydroxylase in modulating the reactivity of cremaster muscle arterioles in normotensive rats on high-salt (HS) and low-salt (LS) diet and in rats with reduced renal mass hypertension (RRM-HT). Changes in arteriolar diameter in response to ACh, sodium nitroprusside (SNP), ANG II, and elevated O2 were measured via television microscopy under control conditions and following cytochrome P-450 v-hydroxylase inhibition with 17-octadecynoic acid (17ODYA) or N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS). In normotensive rats on either LS or HS diet, resting tone was unaffected and arteriolar reactivity to ACh or SNP was minimally affected by cytochrome P-450 v-hydroxylase inhibition. In RRM-HT rats, cytochrome P-450 v-hydroxylase inhibition reduced resting tone and significantly enhanced arteriolar dilation to ACh and SNP. Treatment with 17-ODYA or DDMS inhibited arteriolar constriction to ANG II and O2 in all the groups, although the degree of inhibition was greater in RRM-HT than in normotensive animals. These results suggest that metabolites of cytochrome P-450 v-hydroxylase contribute to the altered reactivity of skeletal muscle arterioles to vasoconstrictor and vasodilator stimuli in RRM-HT.