Forearm vascular responsiveness to alpha 1- and alpha 2-adrenoceptor stimulation in patients with congestive heart failure.
BACKGROUND
The alpha-adrenergic component of the sympathetic nervous system plays a major role in the pathophysiology, clinical manifestations, and natural history of human congestive heart failure (CHF). However, the functional integrity of vascular alpha 1- and alpha 2-adrenoceptors in CHF remains to be elucidated. The present study was designed to assess the vascular responsiveness of alpha 1- and alpha 2-adrenoceptors in patients with CHF.


RESULTS
To evaluate alpha 1- and alpha 2-adrenoceptor responsiveness, we studied the effects of the regional infusion into the brachial artery of increasing doses of phenylephrine (a selective alpha 1-adrenoceptor agonist) and BHT 933 (a selective alpha 2-adrenoceptor agonist) on vascular responses in 12 healthy subjects and in 24 patients with CHF secondary to primary dilated cardiomyopathy or ischemic heart disease. Left ventricular ejection fraction was measured by radionuclide angiography, and forearm blood flow was determined by venous occlusion plethysmography. Phenylephrine reduced forearm blood flow in normal subjects from 5.2 +/- 0.9 to 2.5 +/- 0.6 mL per 100 mL of tissue/min (P < .05) at the highest dose (-50.8 +/- 4.8% versus baseline). A similar vasoconstriction was obtained in patients with CHF (from 3.5 +/- 0.5 to 1.5 +/- 0.2 mL per 100 mL of tissue/min (P < .05) (-58.7 +/- 5.0% versus baseline). The dose-response curves produced by phenylephrine in the two groups were comparable. The highest dose of BHT 933 reduced forearm blood flow in normal subjects from 5.3 +/- 0.9 to 2.3 +/- 0.6 mL per 100 mL of tissue/min (P < .05) (-59.0 +/- 4.9% versus baseline). In patients with CHF, a similar vasoconstriction was obtained (from 4.2 +/- 0.8 to 1.5 +/- 0.3 mL per 100 mL of tissue/min, P < .05, -62.1 +/- 6.5% versus baseline). The dose-response curves produced by BHT 933 also were comparable in the two groups. In patients with CHF, plasma concentrations of norepinephrine were significantly higher than in normal subjects.


CONCLUSIONS
The results of the present study demonstrate that alpha 1- and alpha 2-adrenoceptor stimulations produced an equivalent vasoconstriction in patients with CHF and in normal subjects. This indicates that the vascular responsiveness to alpha-adrenoceptor agonists may be preserved in the limb vessels of patients with CHF.
Indolfi
C
C
Department of Medicine, University Federico II, Naples, Italy.
Maione
A
A
Volpe
M
M
Rapacciuolo
A
A
Esposito
G
G
Ceravolo
R
R
Rendina
V
V
Condorelli
M
M
Chiariello
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001381:Azepines / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D012016:Reference Values
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D010656:Phenylephrine; C015603:azepexole; D009638:Norepinephrine