Effects of dietary calcium on nimodipine-sensitive calcium channel function in stroke-prone spontaneously hypertensive rats.
We studied the effects of dietary Ca2+ on blood pressure, survival, and calcium channel function to investigate cardiovascular disease mechanisms in stroke-prone spontaneously hypertensive rats. Beginning at 3 weeks of age, rats were fed high sodium chloride diets (8.0%) in combination with either high (2.0%) or low (0.2%) Ca2+ diets for 8 weeks. At 12 weeks of age, survival was 90% in the high Ca2+ group and 30% in the low Ca2+ group. The higher blood pressure and lower survival in the low Ca2+ group suggest an intensification of altered vascular muscle cell mechanisms by a dietary Ca2+ deficit. Nimodipine (1-10 nM) effectively blocked L-type Ca2+ currents in isolated vascular muscle cells from both groups. Contraction of isolated cells that were not patch clamped to high potassium solutions were also blocked by 1 nM nimodipine. Disappearance of the L-type Ca2+ channel current was accelerated by holding at depolarizing potentials (positive to -50 mV) and by depolarizing steps to 0 mV. Nimodipine block of the L-type Ca2+ currents in vascular muscle is believed to contribute substantially to antihypertensive properties and stroke prevention, actions that may develop fully only in stroke-prone spontaneously hypertensive rats on a diet of at least normal Ca2+.
Hermsmeyer
K
K
Cardiovascular Research Laboratory, Chiles Research Institute, Providence Medical Center, Portland, OR 97213.
Hatton
D A
DA
Karanja
N
N
McCarron
D
D
D000818:Animals; D001794:Blood Pressure; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000503:physiopathology; D004553:Electric Conductivity; D006973:Hypertension / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D015220:Calcium Channels; D002136:Calcium, Dietary; D009553:Nimodipine