Cyclic nucleotide-dependent regulation of Mn2+ influx, [Ca2+]i, and arterial smooth muscle relaxation.
Elevations in cyclic nucleotide levels can decrease myoplasmic [Ca2+] ([Ca2+]i) and thereby induce arterial smooth muscle relaxation. We evaluated whether cyclic nucleotide-induced reductions in [Ca2+]i are caused by 1) decreased Ca2+ influx or 2) increased Ca2+ sequestration or efflux. Swine carotid medial tissues were loaded with fura-2, and Ca2+ influx was estimated from the quenching rate of 360-nm fluorescence after addition of extracellular Mn2+. Histamine stimulation or high KCl depolarization increased Mn2+ influx, [Ca2+]i, and contractile force. The Ca2+ channel blocker diltiazem attenuated histamine- or KCl-induced increases in Mn2+ influx, [Ca2+]i, and force. Addition of forskolin (which increases cAMP) or nitroglycerin (which increases cGMP) attenuated histamine-induced increases in Mn2+ influx, [Ca2+]i, and force. Addition of forskolin or nitroglycerin also relaxed KCl depolarized tissues; however, Mn2+ influx and [Ca2+]i remained high. These results suggest that Mn(2+)-induced quenching of 360-nm fluorescence is an estimate of Ca2+ influx in the intact swine carotid artery. These results also suggest that cyclic nucleotides can relax swine arterial smooth muscle by at least two mechanisms: 1) reduction of [Ca2+]i primarily induced by decreases in Ca2+ influx and 2) uncoupling force from [Ca2+]i without changing Ca2+ influx or [Ca2+]i.
Chen
X L
XL
Department of Internal Medicine and Physiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Rembold
C M
CM
D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D016257:Fura-2; D008345:Manganese / Q000378:metabolism*; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D009712:Nucleotides, Cyclic / Q000502:physiology*; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D013268:Stimulation, Chemical
D009712:Nucleotides, Cyclic; D008345:Manganese; D011189:Potassium Chloride; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2