Hypertension, Vol 16, 477-483, Copyright © 1990 by American Heart Association
LJ Ignarro
Nitric oxide first captured the interest of biologists when this inorganic
molecule was found to activate cytosolic guanylate cyclase and stimulate
cyclic guanosine monophosphate (GMP) formation in mammalian cells. Further
studies led to the finding that nitric oxide causes vascular smooth muscle
relaxation and inhibition of platelet aggregation by mechanisms involving
cyclic GMP and that several clinically used nitrovasodilators owe their
biological actions to nitric oxide. Nitric oxide possesses physicochemical
and pharmacological properties that make it an ideal candidate for a short-
term regulator or modulator of vascular smooth muscle tone and platelet
function. Nitric oxide is synthesized by various mammalian tissues
including vascular endothelium, macrophages, neutrophils, hepatic Kupffer
cells, adrenal tissue, cerebellum, and other tissues. Nitric oxide is
synthesized from endogenous L-arginine by a nitric oxide synthase system
that possesses different cofactor requirements in different cell types. The
nitric oxide formed diffuses out of its cells of origin and into nearby
target cells, where it binds to the heme group of cytosolic guanylate
cyclase and thereby causes enzyme activation. This interaction represents a
novel and widespread signal transduction mechanism that links extracellular
stimuli to the biosynthesis of cyclic GMP in nearby target cells. The small
molecular size and lipophilic nature of nitric oxide enable communication
with nearby cells containing cytosolic guanylate cyclase. The extent of
transcellular communication is limited by the short half-life of nitric
oxide, thereby ensuring a localized response. Labile nitric oxide-
generating molecules such as S-nitrosothiols may be involved as precursors
or effectors. Further research will provide a deeper understanding of the
biology of nitric oxide and the nature of associated pathophysiological
states.
ARTICLES
Nitric oxide. A novel signal transduction mechanism for transcellular communication
Department of Pharmacology, University of California, School of Medicine, Los Angeles 90024.
This article has been cited by other articles:
 |
|
 |
|
  M. R. Ribeiro and J. C. McNamara Cyclic Guanosine Monophosphate Signaling Cascade Mediates Pigment Aggregation in Freshwater Shrimp Chromatophores Biol. Bull., April 1, 2009; 216(2): 138 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chawengsub, N. T. Aggarwal, K. Nithipatikom, K. M. Gauthier, S. Anjaiah, B. D. Hammock, J. R. Falck, and W. B. Campbell Identification of 15-hydroxy-11,12-epoxyeicosatrienoic acid as a vasoactive 15-lipoxygenase metabolite in rabbit aorta Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1348 - H1356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Fenton and M. A. Knepper Mouse Models and the Urinary Concentrating Mechanism in the New Millennium Physiol Rev, October 1, 2007; 87(4): 1083 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Elia, V. Sander, C.G. Luchetti, M.E. Solano, G. Di Girolamo, C. Gonzalez, and A.B. Motta The mechanisms involved in the action of metformin in regulating ovarian function in hyperandrogenized mice Mol. Hum. Reprod., August 1, 2006; 12(8): 475 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Thompson and Y. Dong Chronic Hypoxia Decreases Endothelial Nitric Oxide Synthease Protein Expression in Fetal Guinea Pig Hearts Reproductive Sciences, September 1, 2005; 12(6): 388 - 395. [Abstract] [PDF]
|
|
|
|
 |
|
 M. P. Guarino, N. C. Correia, W. W. Lautt, and M. P. Macedo Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G527 - G532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Sigmon, E. Gonzalez-Feldman, M. A. Cavasin, D. L. Potter, and W. H. Beierwaltes Role of Nitric Oxide in the Renal Hemodynamic Response to Unilateral Nephrectomy J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1413 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Marchal, A. C. F. Gorren, M. Sorlie, K. K. Andersson, B. Mayer, and R. Lange Evidence of Two Distinct Oxygen Complexes of Reduced Endothelial Nitric Oxide Synthase J. Biol. Chem., May 7, 2004; 279(19): 19824 - 19831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Gauthier, N. Spitzbarth, E. M. Edwards, and W. B. Campbell Apamin-Sensitive K+ Currents Mediate Arachidonic Acid-Induced Relaxations of Rabbit Aorta Hypertension, February 1, 2004; 43(2): 413 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. B. Campbell, N. Spitzbarth, K. M. Gauthier, and S. L. Pfister 11,12,15-Trihydroxyeicosatrienoic acid mediates ACh-induced relaxations in rabbit aorta Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2648 - H2656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chauhan, A. Rahman, H. Nilsson, L. Clapp, R. MacAllister, and A. Ahluwalia NO contributes to EDHF-like responses in rat small arteries: a role for NO stores Cardiovasc Res, January 1, 2003; 57(1): 207 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Wang, M. Patel, H. M. Razavi, S. Weicker, M. G. Joseph, D. G. McCormack, and S. Mehta Role of Inducible Nitric Oxide Synthase in Pulmonary Microvascular Protein Leak in Murine Sepsis Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1634 - 1639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Masuda, T. Tsujii, T. Okuno, K. Kihara, M. Goto, and H. Azuma Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired cavernosal relaxation with ischemia Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1730 - R1738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Newcomb and W. H. Watson III Modulation of swimming in the gastropod Melibe leonina by nitric oxide J. Exp. Biol., February 1, 2002; 205(3): 397 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Uhlenius, O. Vuolteenaho, and I. Tikkanen Renin-angiotensin blockade improves renal cGMP production via non-AT2-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat Journal of Renin-Angiotensin-Aldosterone System, December 1, 2001; 2(4): 233 - 239. [Abstract] [PDF]
|
|
|
|
|
|
H. Sumino, T. Nakamura, T. Kanda, K. Sato, T. Sakamaki, T. Takahashi, Y. Saito, J. Hoshino, T. Kurashina, and R. Nagai Effect of Enalapril on Exhaled Nitric Oxide in Normotensive and Hypertensive Subjects Hypertension, December 1, 2000; 36(6): 934 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kawashima, T. Nagasawa, and H. Ninomiya Contribution of ecto-5'-nucleotidase to the inhibition of platelet aggregation by human endothelial cells Blood, September 15, 2000; 96(6): 2157 - 2162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Whalen, A. K. Johnson, and S. J. Lewis {beta}-Adrenoceptor Dysfunction After Inhibition of NO Synthesis Hypertension, September 1, 2000; 36(3): 376 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-T. DIJKHORST-OEI, P. BOER, T. J. RABELINK, and H. A. KOOMANS Nitric Oxide Synthesis Inhibition Does Not Impair Water Immersion-Induced Renal Vasodilation in Humans J. Am. Soc. Nephrol., July 1, 2000; 11(7): 1293 - 1302. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. W. Wallace and W. L. Tom Interaction of L-Arginine and Phosphodiesterase Inhibitors in Vasodilation of the Porcine Internal Mammary Artery Anesth. Analg., April 1, 2000; 90(4): 840 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D B. Sanders, T. Kelley, and D. Larson The role of nitric oxide synthase/nitric oxide in vascular smooth muscle control Perfusion, March 1, 2000; 15(2): 97 - 104. [Abstract] [PDF]
|
|
|
|
|
|
E. J. Whalen, A. K. Johnson, and S. J. Lewis Tachyphylaxis to PACAP-27 after inhibition of NO synthesis: a loss of adenylate cyclase activation Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1999; 277(5): R1453 - R1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Whalen, M. D. Travis, A. K. Johnson, and S. J. Lewis Rapid tachyphylaxis to hemodynamic effects of PACAP-27 after inhibition of nitric oxide synthesis Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2117 - H2126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G LINDBERG Nitric oxide and the migrating motor complex Gut, January 1, 1999; 44(1): 7 - 7. [Full Text]
|
|
|
|
|
|
W.-C. Lo, C.-R. Jan, S.-N. Wu, and C.-J. Tseng Cardiovascular Effects of Nitric Oxide and Adenosine in the Nucleus Tractus Solitarii of Rats Hypertension, December 1, 1998; 32(6): 1034 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wang and N. Ballatori Endogenous Glutathione Conjugates: Occurrence and Biological Functions Pharmacol. Rev., September 1, 1998; 50(3): 335 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Massett, S. J. Lewis, J. N. Bates, and K. C. Kregel Effect of heating on vascular reactivity in rat mesenteric arteries J Appl Physiol, August 1, 1998; 85(2): 701 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. M. Lynch, D. E. Bruns, J. C. Boyd, and J. Savory Chiron 800 System CO-oximeter Module Overestimates Methemoglobin Concentrations in Neonatal Samples Containing Fetal Hemoglobin Clin. Chem., July 1, 1998; 44(7): 1569 - 1570. [Full Text] [PDF]
|
|
|
|
|
|
E. Colombari, R. L. Davisson, R. A. Shaffer, W. T. Talman, and S. J. Lewis Hemodynamic effects of L-glutamate in NTS of conscious rats: a possible role of vascular nitrosyl factors Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1066 - H1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Carvalho, S. R. Johnson, and N. B. Charan Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta -agonists J Appl Physiol, January 1, 1998; 84(1): 215 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Lash and H. G. Bohlen Time- and order-dependent changes in functional and NO-mediated dilation during exercise training J Appl Physiol, February 1, 1997; 82(2): 460 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamashita, R. A. Schmid, S. Fujino, J. D. Cooper, and G. A. Patterson NICORANDIL, A POTENT ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM-CHANNEL OPENER, AMELIORATES LUNG ALLOGRAFT REPERFUSION INJURY J. Thorac. Cardiovasc. Surg., November 1, 1996; 112(5): 1307 - 1314. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Giulian, L. J. Haverkamp, J. H. Yu, W. Karshin, D. Tom, J. Li, J. Kirkpatrick, Y.-M. Kuo, and A. E. Roher Specific Domains of beta -Amyloid from Alzheimer Plaque Elicit Neuron Killing in Human Microglia J. Neurosci., October 1, 1996; 16(19): 6021 - 6037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Marczin, A. Antonov, A. Papapetropoulos, D. H. Munn, R. Virmani, F. D. Kolodgie, R. Gerrity, and J. D. Catravas Monocyte-Induced Downregulation of Nitric Oxide Synthase in Cultured Aortic Endothelial Cells Arterioscler Thromb Vasc Biol, September 1, 1996; 16(9): 1095 - 1103. [Abstract] [Full Text]
|
|
|
|
|
|
R. L. Davisson, R. A. Shaffer, A. K. Johnson, and S. J. Lewis Use-Dependent Loss of Active Sympathetic Neurogenic Vasodilation After Nitric Oxide Synthase Inhibition in Conscious Rats: Evidence for the Presence of Preformed Stores of Nitric Oxide–Containing Factors Hypertension, September 1, 1996; 28(3): 347 - 353. [Abstract] [Full Text]
|
|
|
|
|
|
R. L. Davisson, J. N. Bates, A. K. Johnson, and S. J. Lewis Use-Dependent Loss of Acetylcholine- and Bradykinin-Mediated Vasodilation After Nitric Oxide Synthase Inhibition: Evidence for Preformed Stores of Nitric Oxide–Containing Factors in Vascular Endothelial Cells Hypertension, September 1, 1996; 28(3): 354 - 360. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. L. Davisson, M. D. Travis, J. N. Bates, and S. J. Lewis Hemodynamic Effects of L- and D-S-Nitrosocysteine in the Rat: Stereoselective S-Nitrosothiol Recognition Sites Circ. Res., August 1, 1996; 79(2): 256 - 262. [Abstract] [Full Text]
|
|
|
|
|
|
M. Tsutsui, S. Milstien, and Z. S. Katusic Effect of Tetrahydrobiopterin on Endothelial Function in Canine Middle Cerebral Arteries Circ. Res., August 1, 1996; 79(2): 336 - 342. [Abstract] [Full Text]
|
|
|
|
|
|
Z.-q. Yan, T. Yokota, W. Zhang, and G. K. Hansson Expression of Inducible Nitric Oxide Synthase Inhibits Platelet Adhesion and Restores Blood Flow in the Injured Artery Circ. Res., July 1, 1996; 79(1): 38 - 44. [Abstract] [Full Text]
|
|
|
|
|
|
S. P. Salas, F. Altermatt, M. Campos, A. Giacaman, and P. Rosso Effects of Long-term Nitric Oxide Synthesis Inhibition on Plasma Volume Expansion and Fetal Growth in the Pregnant Rat Hypertension, December 1, 1995; 26(6): 1019 - 1023. [Abstract] [Full Text]
|
|
|
|
 |
|
 K.W. Park, H.B. Dai, E. Lowenstein, A. Darvish, and F.W. Sellke Isoflurane Attenuates cAMP-Mediated Vasodilation in Rat Microvessels Circulation, November 1, 1995; 92(9): 423 - 427. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Stamler, D. Singel, and J Loscalzo Biochemistry of nitric oxide and its redox-activated forms Science, December 18, 1992; 258(5090): 1898 - 1902. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Takizawa, H. Yoshikawa, M. Yamada, and H. Morita Expression of nitric oxide synthase isoforms and detection of nitric oxide in rat placenta Am J Physiol Cell Physiol, April 1, 2002; 282(4): C762 - C767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tanioka, K. Nakamura, S. Fujimura, M. Yoshida, M. Suzuki-Kusaba, H. Hisa, and S. Satoh Facilitatory role of NO in neural norepinephrine release in the rat kidney Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1436 - R1442. [Abstract] [Full Text] [PDF]
|
|