Salt-induced ANG II suppression impairs the response of cerebral artery smooth muscle cells to prostacyclin.
Recent studies have demonstrated that cerebral arteries from rats fed a high-salt (HS) diet exhibit impaired vasodilation and altered electrophysiological response to reduction in PO2. The present study examined whether an increase in salt intake alters the response of vascular smooth muscle cells (VSMC) to prostacyclin, a crucial mediator of hypoxic dilation in cerebral arteries. VSMC were isolated from cerebral arteries of male Sprague-Dawley rats maintained on an HS (4% NaCl) or a low-salt diet (0.4% NaCl) for 3 days. The stable prostacyclin analog iloprost (10 ng/ml) inhibited serotonin (0.1-10 microM)-induced contractions and the increase in intracellular Ca2+ concentration ([Ca2+]i) in VSMC isolated from arteries of animals fed the low-salt diet. In contrast, iloprost had no effect on serotonin-induced contractions and increases in [Ca2+]i in VSMC isolated from arteries of rats fed the HS diet. Preventing the fall in ANG in rats fed the HS diet by infusion of a low dose of ANG II (5 ng.kg(-1).min(-1) i.v.) restored the inhibitory effect of iloprost on serotonin-induced contractions and increases in [Ca2+]i in VSMC from animals fed the HS diet. These effects were reversed by AT1 receptor blockade with losartan. These results indicate that ANG II suppression secondary to elevated dietary salt intake impairs vascular relaxation and Ca2+ regulation by prostacyclin.
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Jiaxuan
J
Zhu
Ming
M
Yu
Jill
J
Friesema
Tianjian
T
Huang
Richard J
RJ
Roman
Julian H
JH
Lombard
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000031:analogs & derivatives*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016285:Iloprost / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D012701:Serotonin; D012965:Sodium Chloride; D011464:Epoprostenol; D016285:Iloprost; D019808:Losartan; D002118:Calcium