(Hypertension. 1995;26:164-170.)
© 1995 American Heart Association, Inc.
Articles |
Coronary Kinin Generation Mediates Nitric Oxide Release After Angiotensin Receptor Stimulation
From the Departments of Physiology and Pharmacology (A.N.), New York Medical College, Valhalla.
Correspondence to Thomas H. Hintze, PhD, New York Medical College, Valhalla, NY 10595.
Abstract Our goal was to determine whether angiotensin II
(Ang II) and its metabolic fragments release nitric oxide and the
mechanisms by which this occurs in blood vessels from the canine heart.
We incubated 20 mg of microvessels or large coronary arteries in
phosphate-buffered saline for 20 minutes and measured nitrite release.
Nitrite release increased from 27±2 up to 103±5, 145±17, 84±4,
107±16, and 54±4 pmol/mg (P<.05) in response to
10-5 mol/L of Ang I, II, III, IV, and Ang-(1-7),
respectively. The effects of all angiotensins were blocked by
N
-nitro-L-arginine methyl ester
(100 µmol/L), indicating that nitrite was a product of nitric oxide
metabolism, and by Hoe 140 (10 µmol/L), a specific bradykinin
B2 receptor antagonist, indicating a potential role for
local kinin formation. The protease inhibitors aprotinin (10 µmol/L)
and soybean trypsin inhibitor, which block local kinin formation,
inhibited nitrite release by all of the angiotensins. Angiotensin
nonselective (saralasin), type 1–specific (losartan), and type
2–specific (PD 123319) receptor antagonists abolished the nitrite
released in response to all the fragments. Angiotensin type 1 and type
2 and receptors mediate nitrite release after Ang I, II, III, and
Ang-(1-7), whereas only type 2 receptors mediate nitrite release after
Ang IV. Similar results were obtained in large coronary arteries.
In summary, formation of nitrite from coronary microvessels and large
arteries in the normal dog heart in response to angiotensin peptides is
due to the activation of local kinin production in the coronary vessel
wall.
Key Words: receptors, angiotensin • angiotensins • losartan • saralasin • aprotinin • nitrites
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P. Li, M. C. Chappell, C. M. Ferrario, and K. B. Brosnihan Angiotensin-(1-7) Augments Bradykinin-Induced Vasodilation by Competing With ACE and Releasing Nitric Oxide Hypertension, January 1, 1997; 29(1): 394 - 398. [Abstract] [Full Text] [PDF]
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L. V. d'Uscio, P. Moreau, S. Shaw, H. Takase, M. Barton, and T. F. Luscher Effects of Chronic ETA-Receptor Blockade in Angiotensin II-Induced Hypertension Hypertension, January 1, 1997; 29(1): 435 - 441. [Abstract] [Full Text] [PDF]
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P. Gohlke, I. Kuwer, A. Schnell, K. Amann, G. Mall, and T. Unger Blockade of Bradykinin B2 Receptors Prevents the Increase in Capillary Density Induced by Chronic Angiotensin-Converting Enzyme Inhibitor Treatment in Stroke-Prone Spontaneously Hypertensive Rats Hypertension, January 1, 1997; 29(1): 478 - 482. [Abstract] [Full Text] [PDF]
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R. Maeso, J. Navarro-Cid, R. Munoz-Garcia, E. Rodrigo, L. M. Ruilope, V. Lahera, and V. Cachofeiro Losartan Reduces Phenylephrine Constrictor Response in Aortic Rings From Spontaneously Hypertensive Rats: Role of Nitric Oxide and Angiotensin II Type 2 Receptors Hypertension, December 1, 1996; 28(6): 967 - 972. [Abstract] [Full Text]
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R. D. Bernstein, F. Y. Ochoa, X. Xu, P. Forfia, W. Shen, C. I. Thompson, and T. H. Hintze Function and Production of Nitric Oxide in the Coronary Circulation of the Conscious Dog During Exercise Circ. Res., October 1, 1996; 79(4): 840 - 848. [Abstract] [Full Text]
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P. Gohlke, W. Linz, B. A. Scholkens, G. Wiemer, and T. Unger Cardiac and Vascular Effects of Long-term Losartan Treatment in Stroke-Prone Spontaneously Hypertensive Rats Hypertension, September 1, 1996; 28(3): 397 - 402. [Abstract] [Full Text]
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M. R. Kichuk, N. Seyedi, X. Zhang, C. C. Marboe, R. E. Michler, L. J. Addonizio, G. Kaley, A. Nasjletti, and T. H. Hintze Regulation of Nitric Oxide Production in Human Coronary Microvessels and the Contribution of Local Kinin Formation Circulation, July 1, 1996; 94(1): 44 - 51. [Abstract] [Full Text]
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 T. L. Goodfriend, M. E. Elliott, and K. J. Catt Angiotensin Receptors and Their Antagonists N. Engl. J. Med., June 20, 1996; 334(25): 1649 - 1655. [Full Text] [PDF]
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K. B. Brosnihan, P. Li, and C. M. Ferrario Angiotensin-(1-7) Dilates Canine Coronary Arteries Through Kinins and Nitric Oxide Hypertension, March 1, 1996; 27(3): 523 - 528. [Abstract] [Full Text]
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H. G. Llambi, F. Manni, P. L. Padula, O.A. Carretero, and C.M. Taquini Myocardial Contractility Is Modulated by Angiotensin II via Nitric Oxide Hypertension, March 1, 1996; 27(3): 704 - 708. [Abstract] [Full Text]
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H. Guan, V. Cachofeiro, M. L. Pucci, P. M. Kaminski, M. S. Wolin, and A. Nasjletti Nitric Oxide and the Depressor Response to Angiotensin Blockade in Hypertension Hypertension, January 1, 1996; 27(1): 19 - 24. [Abstract] [Full Text]
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