Calcium channel activation in arterioles from genetically hypertensive rats.
Enhanced contractile responsiveness to the calcium channel agonist Bay K 8644 has been documented in large conduit arteries and small muscular arteries from hypertensive rats. The present study examined the effects of Bay K 8644 on the intracellular calcium concentration ([Ca2+]i) in microvessels from stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Using microspectrofluorometry of fura-2, [Ca2+]i was measured in smooth muscle cells localized on arteriolar fragments (15-35 microns external diameter) isolated after collagenase digestion of the pancreas. Resting [Ca2+]i in hypertensive arterioles (94 +/- 6 nM, n = 29) did not differ from that in normotensive vessels (81 +/- 4 nM, n = 40). KCl (50 mM), applied alone and in the presence of Bay K 8644 (30 nM), stimulated increases in [Ca2+]i that were reversed in calcium-free solution and with nifedipine (10 microM), consistent with activation of potential-operated calcium channels. Potassium-induced calcium transients were consistently potentiated by Bay K 8644. The change in [Ca2+]i evoked by KCl alone or in combination with Bay K 8644 did not differ between arterioles from hypertensive and normotensive rats. In 24% of the vessels from hypertensive rats and in 29% of those from normotensive rats, Bay K 8644 evoked an increase in [Ca2+]i that did not differ significantly between the two strains. The findings indicate that, in contrast to observations made in larger arteries, there is no evidence of a functional abnormality in potential-operated calcium channels in very small arterioles from genetically hypertensive rats.
Storm
D S
DS
Department of Physiology, University of Michigan Medical School, Ann Arbor.
Stuenkel
E L
EL
Webb
R C
RC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D010646:Phentolamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism
D015220:Calcium Channels; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D012964:Sodium; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine