title: Contribution of cytochrome P-450 omega-hydroxylase to altered arteriolar reactivity with high-salt diet and hypertension.
abstract: The present study evaluated the contribution of cytochrome P-450 omega-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 O(2) were measured via television microscopy under control conditions and following cytochrome P-450 omega-hydroxylase inhibition with 17-octadecynoic acid (17-ODYA) 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 omega-hydroxylase inhibition. In RRM-HT rats, cytochrome P-450 omega-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 O(2) 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 omega-hydroxylase contribute to the altered reactivity of skeletal muscle arterioles to vasoconstrictor and vasodilator stimuli in RRM-HT.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Frisbee
authors.forename: J R
authors.initials: JR
authors.lastname: Falck
authors.forename: J H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology*; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D006977:Hypertension, Renal / Q000378:metabolism*; D008297:Male; D018715:Microscopy, Video; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000378:metabolism* / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology
chemical_list: D000577:Amides; D002317:Cardiovascular Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D017673:Sodium Chloride, Dietary; D013450:Sulfones; D000804:Angiotensin II; D009599:Nitroprusside; C047008:17-octadecynoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; C117975:DDMS; D006899:Mixed Function Oxygenases; C409986:cytochrome P-450 omega-hydroxylase; D000109:Acetylcholine; D010100:Oxygen