Effects of antihypertensive therapy on the hemodynamics of hypertension: Clinical implications

Clinical Therapeutics (Impact Factor: 2.73). 02/1986; 8(4):382-97.
Source: PubMed


Early essential hypertension is characterized by high cardiac output and normal total peripheral resistance and renal blood flow; in chronic hypertension, total peripheral resistance is elevated, cardiac output is decreased from initial levels, and renal blood flow diminishes as the disease progresses. The various classes of antihypertensive drugs induce different hemodynamic effects to maintain blood pressure control. Long-term administration of all classes of antihypertensive drugs results in a decrease in mean arterial pressure, and most drugs reduce total peripheral resistance. Heart rate and cardiac output generally remain unchanged, but they are decreased after long-term therapy with beta-blockers. Some beta-blockers also reduce renal blood flow. Drugs such as the selective alpha 1-adrenergic blocking agent prazosin, which normalizes the hemodynamic profile of hypertension, appear to be advantageous. In addition, prazosin maintains exercise tolerance at near-normal levels.

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    ABSTRACT: Thirty-seven essential hypertensives received placebo for 3 weeks followed by nifedipine retard (n = 14) or enalapril (n = 13) or doxazosin (n = 10) as monotherapy for 6 weeks and attended study days to evaluate the effects of placebo, first dose, and chronic (1-6 weeks) treatment. On each study day, pressor responses to i.v. infusions of phenylephrine (PE) and angiotensin II (AII) were measured 1.5-3 h after drug administration and the derived PD20 values (dose required to increase mean blood pressure by 20 mm Hg) compared. Each treatment produced comparable reductions in BP. Nifedipine significantly attenuated the pressor responses to AII and PE: for AII, the mean PD20 (ng/kg/min) increased from 8.2 (placebo) to 9.9 (first dose), 13.9 (1 week), and 17.4 (6 weeks). Pressor responsiveness to both AII and PE was unchanged following enalapril: for PE, the mean PD20 (micrograms/kg/min) was 2.1 (placebo), 1.5 (first dose), and 1.5 (6 weeks). Doxazosin produced rightward shifts of the PE pressor dose-response curves but had no effect on responses to AII. The relationship between the simultaneous BP and HR changes during the infusion of PE was used as an index of cardiac baroreflex activity. In contrast to enalapril and doxazosin, which had no effect, nifedipine reduced the slope of the HR/BP relationship from -0.62 (placebo) to -0.38 (first dose) and -0.31 beats/min/mm Hg (6 weeks). For comparable reductions in BP, doxazosin only affects adrenergic mechanisms whereas nifedipine affects both adrenergic and non-adrenergically mediated vasoconstriction. The ACE inhibitor enalapril had no effect on pressor responses to AII and PE.
    No preview · Article · Sep 1990 · Journal of Cardiovascular Pharmacology
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    Full-text · Article · Nov 1992 · Journal of Clinical Investigation
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    ABSTRACT: Noninvasive measurement of hemodynamic parameter was undertaken in 240 patients with untreated primary hypertension using impedance cardiography (ICG) in outpatient clinics. High output was defined as a cardiac index (CI) >3.6 L/minute/m(2) and high resistance was defined as the total peripheral resistance index (TPRI) >2700 dyne·s·m(2)/cm(5). Of all patients, 67% had high-resistance hypertension (high TPRI with normal or low CI), and 16% had high-output hypertension (high CI with normal TPRI). Treatment with β-blockers for high-output hypertension and with calcium channel blockers for high-resistance hypertension reduced blood pressure equally, and restored normal hemodynamic balance, as reported in studies using invasive monitoring methods. These findings suggest that it is appropriate to use noninvasive ICG measurements to guide antihypertensive therapy. Multivariate analysis showed that female gender, tachycardia, and low body mass index (BMI) were associated with high-output hypertension, but age was not. Heterogeneity of hemodynamic parameters is thought to be one of the reasons why the efficacies of antihypertensive agents differ between patients. It may be feasible to predict which antihypertensive agent would be the most effective for a particular patient based on hemodynamic measurements or combination of gender, heart rate, and BMI.
    No preview · Article · Jun 2012 · Clinical and Experimental Hypertension