High-calcium diet enhances vasorelaxation in nitric oxide-deficient hypertension.
Because the effects of calcium supplementation on arterial tone in nitric oxide-deficient hypertension are unknown, we investigated the influence of elevating dietary calcium from 1.1 to 3.0% in Wistar rats treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg. kg(-1). day(-1)) for 8 wk. A high-calcium diet attenuated the development of hypertension induced by L-NAME and abrogated the associated impairments of endothelium-independent mesenteric arterial relaxations to nitroprusside, isoproterenol, and cromakalim. Endothelium-dependent relaxations to acetylcholine during nitric oxide synthase inhibition in vitro were decreased in L-NAME rats and improved by calcium supplementation. The inhibition of cyclooxygenase by diclofenac augmented the responses to acetylcholine in L-NAME rats but not in calcium + L-NAME rats. When hyperpolarization of smooth muscle was prevented by KCl precontraction, the responses to acetylcholine during combined nitric oxide synthase and cyclooxygenase inhibition were similar in all groups. Furthermore, superoxide dismutase enhanced the acetylcholine-induced relaxations in L-NAME rats but not in calcium + L-NAME rats. In conclusion, calcium supplementation reduced blood pressure during chronic nitric oxide synthase inhibition and abrogated the associated impairments in endothelium-dependent and -independent arterial relaxation. The augmented vasorelaxation after increased calcium intake in L-NAME hypertension may be explained by enhanced hyperpolarization and increased sensitivity to nitric oxide in arterial smooth muscle and decreased vascular production of superoxide and vasoconstrictor prostanoids.
Jolma
P
P
Department of Pharmacological Sciences, University of Tampere, Finland.
Kalliovalkama
J
J
Tolvanen
J P
JP
Kööbi
P
P
Kähönen
M
M
Hutri-Kähönen
N
N
Wu
X
X
Pörsti
I
I
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002136:Calcium, Dietary / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; D002136:Calcium, Dietary; D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011189:Potassium Chloride; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine