Regulation of nitric oxide production in human coronary microvessels and the contribution of local kinin formation.
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.


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.
Kichuk
M R
MR
Columbia University, College of Physicians and Surgeons, New York, NY, USA.
Seyedi
N
N
Zhang
X
X
Marboe
C C
CC
Michler
R E
RE
Addonizio
L J
LJ
Kaley
G
G
Nasjletti
A
A
Hintze
T H
TH
D000328:Adult; D002303:Cardiac Output, Low / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007705:Kinins / Q000096:biosynthesis*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D012016:Reference Values
D007705:Kinins; D009573:Nitrites; D009569:Nitric Oxide