Regulation of nitric oxide production in human coronary microvessels and the contribution of local kinin formation
- PMID: 8964116
- DOI: 10.1161/01.cir.94.1.44
Regulation of nitric oxide production in human coronary microvessels and the contribution of local kinin formation
Abstract
Background: The goal of this study was to define the regulation of nitric oxide release by coronary microvessels from the failing and nonfailing human heart and to determine the role of local kinin production in the elaboration of nitric oxide by human coronary microvascular endothelium.
Methods and results: Ten hearts from humans with end-stage heart failure and two hearts from patients without heart failure were harvested at the time of orthotopic cardiac transplantation. Microvessels were sieved and the production of nitrite was determined by the Griess reaction. Microvessels were incubated in the presence of agonists for nitric oxide production (acetylcholine and bradykinin), which caused dose-dependent increases in nitrite, a response that was blocked by NG-nitro-L-arginine methyl ester and receptor-specific antagonists (atropine and HOE 140, respectively). In addition, the production of nitrite by microvessels from the failing heart appeared to be less than that produced by microvessels from the nonfailing heart. Incubation with norepinephrine or the alpha2-adrenergic agonist BHT 920 also caused dose-dependent increases in nitrite production, which were blocked by the B2-receptor antagonist HOE 140. This implicated local kinin synthesis as an intermediate step in the production of nitric oxide in response to alpha2-adrenoceptor stimulation. The production of nitric oxide was also prevented by the addition of serine protease inhibitors, which blocked the action of local kallikrein, again suggesting a role for local kinin synthesis.
Conclusions: Our results indicate that nitric oxide is produced by human coronary microvessels, that nitric oxide production may be reduced but certainly not increased in microvessels from the failing human heart, and that there is active local kinin generation in these blood vessels.
Similar articles
-
Angiotensin-converting enzyme inhibitors promote nitric oxide production in coronary microvessels from failing explanted human hearts.Am J Cardiol. 1997 Aug 4;80(3A):137A-142A. doi: 10.1016/s0002-9149(97)00469-4. Am J Cardiol. 1997. PMID: 9293967
-
Amlodipine promotes kinin-mediated nitric oxide production in coronary microvessels of failing human hearts.Am J Cardiol. 1999 Aug 19;84(4A):27L-33L. doi: 10.1016/s0002-9149(99)00362-8. Am J Cardiol. 1999. PMID: 10480443
-
Role of endothelial kinins in control of coronary nitric oxide production.Hypertension. 1997 Nov;30(5):1105-11. doi: 10.1161/01.hyp.30.5.1105. Hypertension. 1997. PMID: 9369263
-
Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation.Hypertension. 1995 Jul;26(1):164-70. doi: 10.1161/01.hyp.26.1.164. Hypertension. 1995. PMID: 7607720
-
Role of kinins in the pathophysiology of myocardial ischemia. In vitro and in vivo studies.Diabetes. 1996 Jan;45 Suppl 1:S51-8. doi: 10.2337/diab.45.1.s51. Diabetes. 1996. PMID: 8529801 Review.
Cited by
-
Increased Prolylcarboxypeptidase Expression Can Serve as a Biomarker of Senescence in Culture.Molecules. 2024 May 9;29(10):2219. doi: 10.3390/molecules29102219. Molecules. 2024. PMID: 38792081 Free PMC article.
-
Overview of the Assessment of Endothelial Function in Humans.Front Med (Lausanne). 2020 Oct 7;7:542567. doi: 10.3389/fmed.2020.542567. eCollection 2020. Front Med (Lausanne). 2020. PMID: 33117828 Free PMC article. Review.
-
Coronary microvascular dysfunction in women with nonobstructive ischemic heart disease as assessed by positron emission tomography.Cardiovasc Diagn Ther. 2017 Apr;7(2):196-205. doi: 10.21037/cdt.2017.04.08. Cardiovasc Diagn Ther. 2017. PMID: 28540214 Free PMC article. Review.
-
Vascular Tone Regulation Induced by C-Type Natriuretic Peptide: Differences in Endothelium-Dependent and -Independent Mechanisms Involved in Normotensive and Spontaneously Hypertensive Rats.PLoS One. 2016 Dec 9;11(12):e0167817. doi: 10.1371/journal.pone.0167817. eCollection 2016. PLoS One. 2016. PMID: 27936197 Free PMC article.
-
The Human Microcirculation: Regulation of Flow and Beyond.Circ Res. 2016 Jan 8;118(1):157-72. doi: 10.1161/CIRCRESAHA.115.305364. Circ Res. 2016. PMID: 26837746 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources