Sustained contraction to angiotensin II and impaired Ca2+-sequestration in the smooth muscle of stroke-prone spontaneously hypertensive rats.
Contractile response to angiotensin II (AngII) of vascular smooth muscle was compared between 12-week-old, stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). AngII induced phasic and tonic contraction in denuded aortic ring preparation. The phasic contraction was concentration-dependent (AngII 10(-9) to 10(-6) mol/L) and similar in both strains. However, the relaxation after phasic contraction was significantly attenuated in SHRSP compared with that in WKY. To examine the recovery of contractile responses to the repeated stimulation, AngII was applied three times at 20- and 60-min intervals. The first maximal contraction was similar in both strains, but the response to the second stimulation was significantly reduced in SHRSP, compared with all three responses in WKY. These results suggested that Ca2+-sequestration into the Ca2+ store is delayed in SHRSP. Cyclopiazonic acid (10(-5) mol/L), an intracellular Ca2+-pump inhibitor, decreased spontaneous relaxation and increased the sustained contraction in WKY, whereas it did not affect the contraction in SHRSP. Insulin, which modulates tonic contraction by facilitating Ca2+-extrusion, was applied at peak contraction by AngII. It enhanced relaxation after phasic contraction in a concentration-dependent manner in SHRSP, but it did not affect the relaxation in WKY. These results suggest that increased sustained contraction observed in SHRSP reflects at least partly the impaired Ca2+-pump activity leading to hypertension.
Mizuno
H
H
University of Shizuoka, Graduate School of Health Sciences, Japan.
Ikeda
M
M
Harada
M
M
Onda
T
T
Tomita
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid