Intracellular calcium stores and oscillatory contractions in arteries from genetically hypertensive rats.
Strips of tail artery from stroke-prone spontaneously hypertensive rats (SHRSP), but not from normotensive Wistar Kyoto (WKY) rats, exhibit oscillatory activity after stimulation with norepinephrine. In addition, oscillatory activity is observed in response to tetraethylammonium (TEA) in vessels from both SHRSP and WKY rats. Mechanistically, the oscillatory contractions are associated with calcium (Ca2+)-driven action potentials. We have tested the hypothesis that intracellular Ca2+ stores participate in the generation of norepinephrine-induced oscillatory contractions in tail arteries from SHRSP. Additionally, the role of intracellular Ca2+ stores on TEA-induced contractions were evaluated. Contractile force in strips of tail artery from SHRSP and WKY rats was measured, using standard muscle bath procedures, and the effect of interventions that affect the storage of intracellular Ca2+ on the oscillatory contractions was evaluated. Depletion of intracellular Ca2+ stores, with ryanodine, or inhibition of Ca2+ uptake into the sarcoplasmic reticulum (SR), with thapsigargin and cyclopiazonic acid (CPA), did not inhibit oscillatory contractions induced by norepinephrine in SHRSP vessels. However, these agents inhibited the amplitude of TEA-induced contractions in WKY strips. Bay K 8644 and A23187 inhibited TEA-induced oscillatory contractions in WKY vessels. In SHRSP tail artery Bay K 8644 inhibited both norepinephrine and TEA-induced contractions, while A23187 did not have any effect. The phospholipase C inhibitor, NCDC (3X 10(-5) M), blocked oscillatory activity induced by norepinephrine in SHRSP tail artery and TEA-induced oscillations both in SHRSP and WKY vessels. These observations suggest that Ca2+ release and Ca2+ uptake into intracellular Ca2+ stores are not involved in the contraction-relaxation cycles that characterize norepinephrine-induced oscillatory activity in SHRSP tail artery. Similarly, SR Ca2+ stores may modulate but are not essential for TEA-induced oscillatory contractions.
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Department of Pharmacology, University of Sao Paulo, Ribeirao Preto, Brazil.
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002219:Carbamates / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D010507:Periodicity; D048448:Phenylcarbamates; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D013623:Tail / Q000098:blood supply; D019789:Tetraethylammonium / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002219:Carbamates; D004791:Enzyme Inhibitors; D007211:Indoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007476:Ionophores; D048448:Phenylcarbamates; D010726:Phosphodiesterase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D012433:Ryanodine; D000001:Calcimycin; D019789:Tetraethylammonium; D019284:Thapsigargin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid