Effects of deuterium oxide (D2O) on the development of hypertension and Ca2+ homeostasis in spontaneously hypertensive rats.
Increased calcium uptake in vascular tissues, leading to elevated cytosolic free calcium, has been implicated in the pathophysiology of hypertension. In this study we investigated the in vitro effect of deuterium oxide (D2O) on calcium uptake in Sprague-Dawley (SD) rat aortae as well as the effects of 25% D2O, orally administered to spontaneously hypertensive and Wistar-Kyoto (WKY) rats, on systolic blood pressure and aortic calcium uptake. The high calcium uptake induced by phenylephrine (50 mumols/l) via receptor-operated channels and by KCl (80 mmol/l) via voltage-operated channels in SD rat aortae was effectively reduced by D2O in a concentration-dependent manner. These results suggest that D2O, acting like a calcium channel blocker, effectively normalized vascular calcium uptake mechanisms. When, at 7 weeks of age, spontaneously hypertensive rats were given 25% D2O in their drinking water for a period of 6 weeks, the development of high systolic blood pressures and the associated increases in aortic calcium uptake were effectively prevented. D2O treatment did not affect blood pressures in normotensive WKY rats. The parallel increases in systolic blood pressure and in vascular calcium uptake suggest that increased calcium uptake mechanisms are associated with hypertension. Furthermore, D2O appears to prevent hypertension by normalizing calcium uptake in vascular smooth muscle.
Vasdev
S
S
Department of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Sampson
C A
CA
Liepins
A
A
D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003903:Deuterium / Q000494:pharmacology*; D017666:Deuterium Oxide; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors; D014867:Water / Q000494:pharmacology*
D014867:Water; D010656:Phenylephrine; D003903:Deuterium; D017666:Deuterium Oxide; D002118:Calcium