Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation.
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 omega-nitro-L-arginine methyl ester (100 mumol/L), indicating that nitrite was a product of nitric oxide metabolism, and by Hoe 140 (10 mumol/L), a specific bradykinin B2 receptor antagonist, indicating a potential role for local kinin formation. The protease inhibitors aprotinin (10 mumol/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.
Seyedi
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Department of Physiology, New York Medical College, Valhalla 10595, USA.
Xu
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Nasjletti
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Hintze
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TH
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D004285:Dogs; D066298:In Vitro Techniques; D007705:Kinins / Q000378:metabolism*; D008833:Microcirculation / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000187:drug effects*; D013268:Stimulation, Chemical
D057911:Angiotensin Receptor Antagonists; D007705:Kinins; D009573:Nitrites; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D009569:Nitric Oxide; D000803:Angiotensin I; D001120:Arginine; C118790:angiotensin I (1-7); D019331:NG-Nitroarginine Methyl Ester