Cytosolic free calcium of aorta in hypertensive rats. Chronic inhibition of angiotensin converting enzyme.
Cytosolic free calcium concentration ([Ca2+]i) and muscle tension were simultaneously measured in aortic tissue isolated from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) rats, and SHR chronically treated with a novel angiotensin converting enzyme inhibitor, CS-622. In the presence of 2.5 mM Ca2+ in the bathing solution, aortic [Ca2+]i measured with fura-2 was higher in SHR than in WKY rats, and it was almost the same in CS-622-treated SHR and untreated WKY rats. Increase of external Ca2+ concentration from zero to 2.5 mM elicited a contraction in SHR aortas but not in aortas from both CS-622-treated SHR and untreated WKY rats. When the aortas were contracted by 60 mM K+, however, [Ca2+]i as well as developed tension was similar in the three groups. CGP-28392 (10(-6) M), a Ca2+ channel activator, induced a rhythmic activity superimposed on a gradual increase of [Ca2+]i and tension in SHR aortas but not in the aortas of CS-622-treated SHR or untreated WKY rats. Nicardipine (10(-7) M) decreased the resting [Ca2+]i and the resting tone in SHR aortas, but not in WKY rat aortas. These results suggest that SHR aortas have a higher myogenic tone due to increased [Ca2+]i than WKY rat aortas and that the increased [Ca2+]i is attributed to alterations of dihydropyridine-sensitive Ca2+ channels in SHR aortas. Further, the decrease of the vascular tone induced by long-term administration of the angiotensin converting enzyme inhibitor may be due to a reduction of increased [Ca2+]i in SHR.
Cardiovascular Division, Sankyo Co., Ltd., Tokyo, Japan.
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Sada
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Koike
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Ikeda
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Sato
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Ozaki
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Karaki
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000032:analysis* / Q000187:drug effects; D002118:Calcium / Q000032:analysis*; D003600:Cytosol / Q000032:analysis; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013841:Thiazepines / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011725:Pyridines; D013841:Thiazepines; C040525:CGP 28392; C055603:temocapril hydrochloride; D009529:Nicardipine; D002118:Calcium