Alterations of alpha-adrenergic modulations of coronary microvascular tone in dogs with heart failure.
BACKGROUND
It remains unclear whether coronary microvascular response to alpha-adrenergic activation alters in chronic heart failure (CHF).


RESULTS
We investigated the alpha-adrenergic receptor-mediated effects on coronary pressure-flow relationship (CPFR) in a tachycardia-induced canine heart failure model. The dogs studied were male (29 of 31) and the drugs were given intracoronary. The slope of CPFR during long diastole was evaluated as an index of coronary vascular resistance, during alpha1- or alpha2-adrenergic stimulation or inhibition under anesthesia in the baseline and failing state after 3 weeks of rapid ventricular pacing. Resting coronary blood flow and CPFR did not change in the failing state from the baseline state. Neither alpha1 nor alpha2 stimulation changed the slope of CPFR in the baseline state. However, in the failing state, alpha1 stimulation decreased the slope of CPFR by 23 +/- 5% (P < .05), whereas alpha2 stimulation increased it by 73 +/- 10% (P < .05), which was nearly abolished by pretreatment with NG-nitro-L-arginine methyl ester.


CONCLUSIONS
Alpha2-mediated vasodilatory action, presumably via endothelium-derived nitric oxide release, would be enhanced in the coronary microvascular bed, which may antagonize enhanced alpha1-induced vasoconstriction in CHF.
Tamagawa
Kazuaki
K
First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
Saito
Tomiyoshi
T
Oikawa
Yuji
Y
Maehara
Kazuhira
K
Yaoita
Hiroyuki
H
Maruyama
Yukio
Y
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002932:Cineangiography; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D011433:Propranolol / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology; D015016:Yohimbine / Q000008:administration & dosage
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C018176:bunazosin; D011433:Propranolol; D019331:NG-Nitroarginine Methyl Ester