Reversal of hypertension and endothelial dysfunction in deoxycorticosterone-NaCl-treated rats by high-Ca2+ diet.
We tested the effect of high-Ca2+ diet on blood pressure and responses of mesenteric arterial rings in vitro in established deoxycorticosterone (DOC)-NaCl hypertension. Ca2+ supplementation (2.5%) of Wistar rats, which was commenced 8 wk after initiation of DOC-NaCl treatment (Ca(2+)-DOC group), reversed the development of hypertension, whereas in animals ingesting a normal diet (1.1% Ca2+; DOC group) blood pressure continued to rise until the end of the 12-wk study. In norepinephrine-precontracted arterial rings, relaxations to acetylcholine (ACh) and sodium nitroprusside were attenuated in the DOC group, but these responses were significantly improved by Ca2+ supplementation. The nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester, in the presence of diclofenac, totally abolished ACh-induced relaxations in the DOC group but only attenuated them in the Ca(2+)-DOC group. The remaining relaxation was further inhibited by apamin, an inhibitor of Ca(2+)-activated K+ channels, and practically abolished after blockade of ATP-dependent K+ channels by glyburide. Interestingly, when endothelium-dependent hyperpolarization was prevented using precontractions induced by KCl, no differences were found in relaxations to ACh between the groups. In conclusion, high-Ca(2+) diet effectively reduced blood pressure in DOC-NaCl hypertension and concomitantly enhanced arterial relaxation. Because the relaxations to ACh in the Ca(2+)-DOC group were augmented in the absence and presence of NO synthesis inhibition but not under conditions of prevented hyperpolarization, these enhanced relaxations could be attributed to promoted endothelium-dependent hyperpolarization in the Ca(2+)-supplemented animals.
Mäkynen
H
H
Department of Pharmacology, Clinical Pharmacology and Toxicology, Medical School, University of Tampere, Finland.
Kähönen
M
M
Wu
X
X
Wuorela
H
H
Pörsti
I
I
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002136:Calcium, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D003900:Desoxycorticosterone; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride
D002136:Calcium, Dietary; D003900:Desoxycorticosterone; D012965:Sodium Chloride