Background: A synergistic interaction between the angiotensin II (Ang II) type 1 receptor and alpha1-adrenergic receptors has been described. We hypothesized that the nonselective beta-antagonist carvedilol, through its alpha1-adrenergic blocking properties, may modulate vascular reactivity to Ang II in patients with chronic heart failure (CHF). Accordingly, we compared the vasopressor response to infused Ang II in patients treated with carvedilol and metoprolol, a selective beta-antagonist.
Methods and results: All subjects were treated with carvedilol or metoprolol for at least 3 months. ACE inhibitor therapy was standardized to enalapril 40 mg/d or the maximally tolerated dose. Exogenous Ang II was administered as sequential intravenous bolus injections (2.5 to 30 ng/kg) titrated to a rise in radial artery systolic pressure of > or =20 mm Hg. The dose of Ang II required to elicit a change of 20 mm Hg in radial artery systolic pressure (PD20) defined the vasopressor response to Ang II. Twenty subjects with CHF (mean left ventricular ejection fraction 28+/-9%, New York Heart Association class II [n=13] and III [n=7]) were studied. There was no correlation between plasma Ang II levels and PD20. However, the PD20 was significantly higher in patients treated with carvedilol than in those treated with metoprolol (20 [range 2.5 to 30] versus 5 [range 2.5 to 10] ng/kg, P=0.019).
Conclusions: The vasopressor response to Ang II infusion in patients treated with carvedilol was significantly lower than in patients treated with metoprolol. Whether this is due to the alpha1-adrenergic blocking or other ancillary properties of carvedilol warrants further investigation.