title: Chronic AT(1) receptor blockade alters mechanisms mediating responses to hypoxia in rat skeletal muscle resistance arteries.
abstract: The goal of this study was to determine the effect of angiotensin type 1 (AT(1)) receptor antagonism on vasodilator responses in isolated skeletal muscle resistance arteries. Normotensive Sprague-Dawley rats were fed normal rat chow with the AT(1) receptor antagonist losartan (1mg/ml) in the drinking water for 7 days and compared with untreated control rats. Changes in the diameter of isolated resistance arteries supplying the gracilis muscle were assessed with a video micrometer. Arteriolar responses to acetylcholine, iloprost, and sodium nitroprusside were unaffected by losartan administration, whereas dilation to reduced Po(2) was converted into a constriction. Hypoxia-induced constriction of vessels from losartan-treated rats was inhibited by endothelium removal or indomethacin (1 microM). Blockade of the PGH(2)-thromboxane A(2) receptor with SQ-29548 (10 microM), thromboxane synthase inhibition with dazoxiben (10 microM), or the addition of the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL, 100 microM) converted hypoxic vasoconstriction to a dilation that was blocked by inhibiting nitric oxide synthase with N(omega)-nitro-l-arginine methyl ester (100 microM). These data suggest that AT(1) receptor activation has an important role in maintaining the vascular release of prostaglandins responsible for mediating hypoxic dilation in skeletal muscle microvessels.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Phillips
authors.forename: Ines
authors.initials: I
authors.lastname: Drenjancevic-Peric
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D013997:Time Factors; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013931:Thromboxanes; D014665:Vasodilator Agents; D013928:Thromboxane A2; D011464:Epoprostenol; D019808:Losartan; D000109:Acetylcholine; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin