Angiotensin II AT1 receptors preserve vasodilator reactivity in skeletal muscle resistance arteries.
Resistance arteries (100-150 microm) were isolated from the gracilis muscle of normotensive Sprague-Dawley rats placed on a high-salt (HS) diet (4.0% NaCl) for 3-7 days. Exposure to the HS diet eliminated vascular relaxation in response to hypoxia (PO2 reduction to 35-40 Torr) and iloprost, a stable analog of prostacyclin. Vasodilator responses were restored in arteries isolated from chronically instrumented HS rats receiving a continuous intravenous infusion of either angiotensin II (ANG II; 5-6 ng x kg(-1) x min(-1)) or ANG II plus the AT2 receptor blocker PD-123319 (5 microg x kg(-1) x min(-1)) for 3 days before the isolated vessel studies. In contrast, coinfusion of the AT1 receptor blocker losartan (20 microg x kg(-1) x min(-1)) or coinfusion of both receptor blockers with ANG II eliminated the protective effect of ANG II to restore dilator responses to hypoxia and iloprost. Neither a HS diet nor ANG II infusion affected the dilation of gracilis arteries in response to direct activation of adenylyl cyclase by forskolin, suggesting that the effect of both the HS diet and the ANG II on the vasculature is mediated upstream from second messenger systems. These findings indicate that the protective effect of ANG II to maintain vasodilator reactivity in resistance arteries of rats on a HS diet is mediated via the AT1 receptor subtype.
Weber
D S
DS
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Lombard
J H
JH
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001795:Blood Pressure Determination; D003243:Consciousness; D016285:Iloprost / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012982:Sodium, Dietary / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; C073402:PD 123319; D016285:Iloprost; D019808:Losartan; D010100:Oxygen