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.
[Show abstract][Hide abstract] ABSTRACT: Chronic administration of alpha 1-receptor antagonists is associated with loss of clinical efficacy, especially in congestive heart failure, although the mechanism is uncertain. To evaluate changes in venous alpha 1-adrenoceptor responsiveness during chronic alpha 1-adrenoceptor blockade, dose-response curves to phenylephrine and angiotensin II were constructed in 10 healthy subjects before, during, and after administration of terazosin 1 mg orally for 28 d. Terazosin initially shifted the dose-response curve of phenylephrine to the right, with a significant increase in ED50 for phenylephrine from a control value of 102 to 759 ng/min on day 1 of terazosin (P < 0.001). However, by day 28, the dose-response curve had shifted back towards baseline with an ED50 of 112 ng/min. After discontinuing terazosin, the ED50 for phenylephrine remained near the baseline value, indicating no evidence of supersensitivity to phenylephrine. There was no change in responsiveness to angiotensin II during the course of treatment with terazosin. Plasma terazosin concentrations were stable throughout the period of drug administration. The mean Kd of terazosin was estimated as 11 +/- 15 nM in the first few days of treatment. This study demonstrates that pharmacological tolerance to the alpha 1-adrenoceptor blocking action of terazosin occurs in man and may be responsible for loss in efficacy with chronic therapy.
[Show abstract][Hide abstract] 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.
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