Chronic AT(1) receptor blockade alters mechanisms mediating responses to hypoxia in rat skeletal muscle resistance arteries. Am J Physiol Heart Circ Physiol 2004 Aug;287(2):H545-52
Date
03/27/2004Pubmed ID
15044197DOI
10.1152/ajpheart.01098.2003Scopus ID
2-s2.0-3242710400 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
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.
Author List
Phillips SA, Drenjancevic-Peric I, Frisbee JC, Lombard JHMESH terms used to index this publication - Major topics in bold
AcetylcholineAngiotensin II Type 1 Receptor Blockers
Animals
Arteries
Cardiovascular Agents
Enzyme Inhibitors
Epoprostenol
Hypoxia
In Vitro Techniques
Indomethacin
Losartan
Male
Muscle, Skeletal
NG-Nitroarginine Methyl Ester
Oxygen
Partial Pressure
Rats
Rats, Sprague-Dawley
Receptors, Thromboxane A2, Prostaglandin H2
Thromboxane A2
Thromboxanes
Time Factors
Vascular Resistance
Vasoconstriction
Vasodilation
Vasodilator Agents
