Alpha adrenergic blockade by prazosin in therapy of essential hypertension

Abstract

To elucidate the mechanism of action of prazosin in lowering the blood pressure, we studied the vascular pressor responsiveness to the infusion of norepinephrine and angiotensin II before and after prazosin in patients with essential hypertension. After prazosin, the pressor response to the alpha agonist norepinephrine was markedly attenuated, but the vascular reactivity to angiotensin II was unchanged. There was a threefold increment in the dose of norepinephrine required to elicit a 20 mm Hg rise in diastolic blood pressure after prazosin therapy. These results confirm that prazosin induces significant alpha adrenergic blockade during the treatment of essential hypertension. Clinical Pharmacology and Therapeutics (1981) 29, 719–722; doi:

Alpha-Adrenergic Mechanisms in the Cardiovascular Hyperreactivity to Norepinephrine-Infusion in Essential Hypertension

“…In HT, cardiovascular reactivity to NEinfusion after a-AR blockade has been only investigated using selective a 1 -AR blockade. Here, two studies in HT only found diminished mean arterial BP (MAP) reactivity (24) as well as diminished DBP responsiveness (25) to NE-infusion after selective a 1 -AR blockade as compared to placebo, while HR reactivity to NE-infusion did not differ between a 1 -AR blockade and placebo condition (24). Taken together, in the context of cardiovascular reactivity to either stress or catecholamineinfusion, studies using non-selective a-AR blockade are lacking in HT and a-AR functioning has not yet been compared between HT and NT.…”

“…Our DBP results are in line with previous literature in either HT or NT. In HT, higher NE dosages were required to induce DBP-increases of 20 mmHg after a 1 -AR blockade (25) and MAP reactivity to NE-infusion was attenuated after a 1 -AR blockade (24), both as compared to placebo. Notably, DBP has a stronger impact on calculated MAP (MAP=2/3 DBP+1/3 SBP) than SBP.…”

PKPD modelling of the interrelationship between mean arterial BP, cardiac output and total peripheral resistance in conscious rats

“…We have selected a training set of six antihypertensive compounds with different, but well described effects on CO and/or TPR: enalapril, fasudil, amlodipine, prazosin, propranolol and hydrochlorothiazide (HCTZ) to challenge the CVS. The first four compounds have their primary effect on TPR; whereas the latter two compounds have their primary effect on CO (Ram et al, 1981;Cleophas, 1998;Masumoto et al, 2001). An overview of the mechanisms of action (MoA) of these compounds can be found in Table 1.…”