BACKGROUND: Resistance, pulse wave velocity, and wave reflections have been shown to be increased in patients with essential hypertension compared with normotensive controls. These alterations are completely normalized by nitroprusside infusion but exacerbated during beta-adrenergic blockade, suggesting an enhanced smooth muscle tone that is in part modulated by adrenergically mediated vasodilation. The present study was performed to examine the extent to which this apparently enhanced smooth muscle tone is a result of alpha-adrenergically mediated vasoconstriction. METHODS AND RESULTS: Age-matched normotensive and hypertensive Chinese subjects were instrumented with catheter-tipped micromanometers and an electromagnetic flow velocity sensor positioned in the ascending aorta. Aortic impedance and wave reflection properties were obtained from Fourier analysis of the pressure and flow signals during baseline conditions, after beta-blockade with propranolol (0.15 mg/kg i.v.), and after alpha-blockade with intravenous phentolamine (range, 15-80 mg) that was sufficient to either normalize blood pressure or produce a pressure that could not be further lowered. Compared with normotensives, in the baseline state, hypertensives had elevated resistance (1,962 versus 1,268 dyne.sec/cm5, p less than 0.001), total power (1,893 versus 1,568 mW, p less than 0.08), reflected pressure wave component (25.6 versus 13.5 mm Hg, p less than 0.001), ratio of reflected to forward wave (0.65 versus 0.42, p less than 0.001), and pulse wave velocity as determined from the frequency of the first zero-crossing of impedance phase angle (4.6 versus 3.5 Hz, p less than 0.03). During combined alpha- and beta-adrenergic blockade, blood pressure decreased into the normal range (from 162/103 to 131/87 mm Hg) but was still somewhat higher than that in the normotensive subjects. Resistance (1,914 dyne.sec/cm5, p less than 0.03), reflected wave (19.5 mm Hg, p less than 0.01), and ratio of reflected to forward wave (0.61, p less than 0.001) were, however, persistently elevated above normal values. CONCLUSIONS: alpha-Adrenergically mediated vasoconstriction cannot account for all of the hemodynamic alterations seen in essential hypertension.
BACKGROUND: Resistance, pulse wave velocity, and wave reflections have been shown to be increased in patients with essential hypertension compared with normotensive controls. These alterations are completely normalized by nitroprusside infusion but exacerbated during beta-adrenergic blockade, suggesting an enhanced smooth muscle tone that is in part modulated by adrenergically mediated vasodilation. The present study was performed to examine the extent to which this apparently enhanced smooth muscle tone is a result of alpha-adrenergically mediated vasoconstriction. METHODS AND RESULTS: Age-matched normotensive and hypertensive Chinese subjects were instrumented with catheter-tipped micromanometers and an electromagnetic flow velocity sensor positioned in the ascending aorta. Aortic impedance and wave reflection properties were obtained from Fourier analysis of the pressure and flow signals during baseline conditions, after beta-blockade with propranolol (0.15 mg/kg i.v.), and after alpha-blockade with intravenous phentolamine (range, 15-80 mg) that was sufficient to either normalize blood pressure or produce a pressure that could not be further lowered. Compared with normotensives, in the baseline state, hypertensives had elevated resistance (1,962 versus 1,268 dyne.sec/cm5, p less than 0.001), total power (1,893 versus 1,568 mW, p less than 0.08), reflected pressure wave component (25.6 versus 13.5 mm Hg, p less than 0.001), ratio of reflected to forward wave (0.65 versus 0.42, p less than 0.001), and pulse wave velocity as determined from the frequency of the first zero-crossing of impedance phase angle (4.6 versus 3.5 Hz, p less than 0.03). During combined alpha- and beta-adrenergic blockade, blood pressure decreased into the normal range (from 162/103 to 131/87 mm Hg) but was still somewhat higher than that in the normotensive subjects. Resistance (1,914 dyne.sec/cm5, p less than 0.03), reflected wave (19.5 mm Hg, p less than 0.01), and ratio of reflected to forward wave (0.61, p less than 0.001) were, however, persistently elevated above normal values. CONCLUSIONS: alpha-Adrenergically mediated vasoconstriction cannot account for all of the hemodynamic alterations seen in essential hypertension.
Authors: James A Cockburn; Sally E Brett; Antoine Guilcher; Albert Ferro; James M Ritter; Philip J Chowienczyk Journal: Br J Clin Pharmacol Date: 2010-04 Impact factor: 4.335