Circulation Research, Vol 62, 961-964, Copyright © 1988 by American Heart Association

ARTICLES

Cyclic guanosine monophosphate-enhanced sequestration of Ca2+ by sarcoplasmic reticulum in vascular smooth muscle

CH Twort and C van Breemen
Department of Pharmacology, University of Miami School of Medicine, Florida.

The purpose of this study was to investigate the effects of the intracellular messenger cyclic GMP (cGMP) on sequestration of cytosolic calcium (Ca2+) into the intracellular Ca2+ store (the sarcoplasmic reticulum) of vascular smooth muscle. Using saponin-skinned primary cultures of rat aortic smooth muscle, we investigated the effect of cGMP on 45Ca uptake in monolayers of cells. The intracellular store was loaded with Ca2+ by exposing the skinned cells to a 45Ca-labeled 1- microM free Ca2+-containing solution for varying durations (0-20 minutes). Addition of 10 microM cGMP to six monolayers increased both the initial Ca2+ uptake at 2 minutes (control, 240 +/- 8 pmol Ca2+/10(6) cells; + cGMP 295 +/- 7; mean +/- SEM; n = 6, p less than 0.01) and the final steady-state uptake reached at 20 minutes (control, 0.96 +/- 0.03 nmol Ca2+/10(6) cells; + cGMP 1.12 +/- 0.03, p less than 0.02). This stimulation of uptake was quantitatively similar to that caused by 10 microM cyclic AMP. It occurred at varying ambient cytosolic Ca2+ concentrations (0.1-1.0 microM Ca2+) and was not further enhanced by addition of 10 microM cGMP-dependent protein kinase. The dose-response of stimulation of Ca2+ uptake with cGMP indicated an ED50 of 5 nM cGMP. The release of Ca2+ from the sarcoplasmic reticulum in response to inositol 1,4,5-trisphosphate or caffeine was unaffected by cGMP. We conclude that the relaxation of vascular smooth muscle with cGMP-producing vasodilators is mediated in part by sequestration of cytosolic Ca2+ by the sarcoplasmic reticulum.

This article has been cited by other articles:

				T. Kitazawa, S. Semba, Y. H. Huh, K. Kitazawa, and M. Eto Nitric oxide-induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI-17 and MYPT1 J. Physiol., July 15, 2009; 587(14): 3587 - 3603. [Abstract] [Full Text] [PDF]

				F. S. GRAGASIN, E. D. MICHELAKIS, A. HOGAN, R. MOUDGIL, K. HASHIMOTO, X. WU, S. BONNET, A. HAROMY, and S. L. ARCHER The neurovascular mechanism of clitoral erection: nitric oxide and cGMP-stimulated activation of BKCa channels FASEB J, September 1, 2004; 18(12): 1382 - 1391. [Abstract] [Full Text] [PDF]

				S. Komatsu, K. Miyazaki, R. A. Tuft, and M. Ikebe Translocation of telokin by cGMP signaling in smooth muscle cells Am J Physiol Cell Physiol, September 1, 2002; 283(3): C752 - C761. [Abstract] [Full Text] [PDF]

				E. N Dedkova and L. A Blatter Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells J. Physiol., February 15, 2002; 539(1): 77 - 91. [Abstract] [Full Text] [PDF]

				Z. Ungvari and A. Koller Signal Transduction in Smooth Muscle: Selected Contribution: NO released to flow reduces myogenic tone of skeletal muscle arterioles by decreasing smooth muscle Ca2+ sensitivity J Appl Physiol, July 1, 2001; 91(1): 522 - 527. [Abstract] [Full Text] [PDF]

				S. M. Nauli, L. Zhang, and W. J. Pearce Maturation depresses cGMP-mediated decreases in [Ca2+]i and Ca2+ sensitivity in ovine cranial arteries Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1019 - H1028. [Abstract] [Full Text] [PDF]

				V. Hampl and J. Herget Role of Nitric Oxide in the Pathogenesis of Chronic Pulmonary Hypertension Physiol Rev, October 1, 2000; 80(4): 1337 - 1372. [Abstract] [Full Text] [PDF]

				C.-W. Sun, J. R. Falck, H. Okamoto, D. R. Harder, and R. J. Roman Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat cerebral arteries Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H339 - H350. [Abstract] [Full Text] [PDF]

				C. Mundina-Weilenmann, L. Vittone, G. Rinaldi, M. Said, G. C. de Cingolani, and A. Mattiazzi Endoplasmic reticulum contribution to the relaxant effect of cGMP- and cAMP-elevating agents in feline aorta Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1856 - H1865. [Abstract] [Full Text] [PDF]

				I. A. Buhimschi, C. Yallampalli, C. S. Buhimschi, G. R. Saade, and R. E. Garfield Distinct regulation of nitric oxide and cyclic guanosine monophosphate production by steroid hormones in the rat uterus Mol. Hum. Reprod., May 1, 2000; 6(5): 404 - 414. [Abstract] [Full Text] [PDF]

				J. E. Seiden, O. Platoshyn, A. E. Bakst, S. S. McDaniel, and J. X.-J. Yuan High K+-induced membrane depolarization attenuates endothelium-dependent pulmonary vasodilation Am J Physiol Lung Cell Mol Physiol, February 1, 2000; 278(2): L261 - L267. [Abstract] [Full Text] [PDF]

				M. S. Taylor, H. Gao, J. D. Gardner, and J. N. Benoit Effects of IBMX on norepinephrine-induced vasoconstriction in small mesenteric arteries Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G909 - G914. [Abstract] [Full Text] [PDF]

				K. S. Murthy and G. M. Makhlouf Differential Regulation of Phospholipase A2 (PLA2)-dependent Ca2+ Signaling in Smooth Muscle by cAMP- and cGMP-dependent Protein Kinases. INHIBITORY PHOSPHORYLATION OF PLA2 BY CYCLIC NUCLEOTIDE-DEPENDENT PROTEIN KINASES J. Biol. Chem., December 18, 1998; 273(51): 34519 - 34526. [Abstract] [Full Text] [PDF]

				C.-W. Sun, M. Alonso-Galicia, M. R. Taheri, J. R. Falck, D. R. Harder, and R. J. Roman Nitric Oxide-20–Hydroxyeicosatetraenoic Acid Interaction in the Regulation of K+ Channel Activity and Vascular Tone in Renal Arterioles Circ. Res., November 30, 1998; 83(11): 1069 - 1079. [Abstract] [Full Text] [PDF]

				K. S. Murthy and G. M. Makhlouf cGMP-mediated Ca2+ release from IP3-insensitive Ca2+ stores in smooth muscle Am J Physiol Cell Physiol, May 1, 1998; 274(5): C1199 - C1205. [Abstract] [Full Text] [PDF]

				G. Kojda, M. Patzner, A. Hacker, and E. Noack Nitric Oxide Inhibits Vascular Bioactivation of Glyceryl Trinitrate: A Novel Mechanism to Explain Preferential Venodilation of Organic Nitrates Mol. Pharmacol., March 1, 1998; 53(3): 547 - 554. [Abstract] [Full Text]

				C. M. Rembold and X.-L. Chen Mechanisms Responsible for Forskolin-Induced Relaxation of Rat Tail Artery Hypertension, March 1, 1998; 31(3): 872 - 877. [Abstract] [Full Text] [PDF]

				M. A. Nazer and C. Van Breemen A role for the sarcoplasmic reticulum in Ca2+ extrusion from rabbit inferior vena cava smooth muscle Am J Physiol Heart Circ Physiol, January 1, 1998; 274(1): H123 - H131. [Abstract] [Full Text] [PDF]

				B. Tonshoff, F. J. Kaskel, and L. C. Moore Effects of insulin-like growth factor I on the renal juxtamedullary microvasculature Am J Physiol Renal Physiol, January 1, 1998; 274(1): F120 - F128. [Abstract] [Full Text] [PDF]

				M. Cappelli-Bigazzi, G. Ambrosio, G. Musci, C. Battaglia, M. C. B. Di Patti, P. Golino, M. Ragni, M. Chiariello, and L. Calabrese Ceruloplasmin impairs endothelium-dependent relaxation of rabbit aorta Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2843 - H2849. [Abstract] [Full Text] [PDF]

				D. Henrion, F. J. Dowell, B. I. Levy, and J.-B. Michel In Vitro Alteration of Aortic Vascular Reactivity in Hypertension Induced by Chronic NG-Nitro-L-Arginine Methyl Ester Hypertension, September 1, 1996; 28(3): 361 - 366. [Abstract] [Full Text]

				S. L. Archer, J. M.C. Huang, H. L. Reeve, V. Hampl, S. Tolarova, E. Michelakis, and E. K. Weir Differential Distribution of Electrophysiologically Distinct Myocytes in Conduit and Resistance Arteries Determines Their Response to Nitric Oxide and Hypoxia Circ. Res., March 1, 1996; 78(3): 431 - 442. [Abstract] [Full Text]

				R. A. Cohen and P. M. Vanhoutte Endothelium-Dependent Hyperpolarization : Beyond Nitric Oxide and Cyclic GMP Circulation, December 1, 1995; 92(11): 3337 - 3349. [Full Text]

				S. L. Archer, K. A. Freude, and P. J. Shultz Effect of Graded Hypoxia on the Induction and Function of Inducible Nitric Oxide Synthase in Rat Mesangial Cells Circ. Res., July 1, 1995; 77(1): 21 - 28. [Abstract] [Full Text]

				O. Zolle, A. M. Lawrie, and A. W. M. Simpson Activation of the Particulate and Not the Soluble Guanylate Cyclase Leads to the Inhibition of Ca2+ Extrusion through Localized Elevation of cGMP J. Biol. Chem., August 18, 2000; 275(34): 25892 - 25899. [Abstract] [Full Text] [PDF]

				M. Yu, C.-W. Sun, K. G. Maier, D. R. Harder, and R. J. Roman Mechanism of cGMP contribution to the vasodilator response to NO in rat middle cerebral arteries Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1724 - H1731. [Abstract] [Full Text] [PDF]