Role of nitric oxide in impaired coronary circulation and improvement by angiotensin II receptor antagonist in spontaneously hypertensive rats.
1. To determine whether coronary flow regulation by nitric oxide (NO) is impaired in the hypertensive heart (HTH), coronary perfusion was measured in isolated rat hearts using NO synthesis inhibitor L-NG-monomethyl arginine (L-NMMA) in Wistar-Kyoto (WKY) rat and spontaneously hypertensive rat (SHR) with and without chronic Nomega-nitro-L-arginine-methylester (L-NAME) treatment. Moreover, the effect of angiotensin II receptor antagonist (AT1 receptor antagonist) (TCV-116) on the impaired coronary circulation in HTH was examined. 2. Coronary flow (CF) was decreased in HTH accompanied with cardiac hypertrophy. The decreased response of CF to L-NMMA infusion was diminished in HTH. It is suggested that NO production was reduced in coronary vasculature in HTH. 3. In chronic L-NAME treated SHR, blood pressure and cardiac hypertrophy were accelerated. Although coronary flow resistance (CFR) was increased, the increased response of CFR to L-NMMA infusion was not altered. 4. The AT1 antagonist improved total minimal coronary flow resistance (MCFR) restoring CFR response in SHR, although it did not recover CFR response in chronic L-NAME treated SHR. 5. Taken together the findings suggest that NO production was exhausted in the coronary artery even in the developing stage of hypertension and this exhaustion could contribute to the impairment of coronary circulation of HTH.
Fujita
H
H
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Takeda
K
K
Nakamura
K
K
Uchida
A
A
Takenaka
K
K
Itoh
H
H
Nakata
T
T
Sasaki
S
S
Nakagawa
M
M
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C077793:candesartan cilexetil; D019331:NG-Nitroarginine Methyl Ester