Abstract
Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca++-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents.
Highlights
IntroductionThe long-term regulation of systemic arterial blood pressure is a topic beset with a remarkable degree of controversy
Why Is This Topic Currently Especially Important?The long-term regulation of systemic arterial blood pressure is a topic beset with a remarkable degree of controversy
In the tables below we present statistically significant changes in renal hemodynamic variables or indicate no change
Summary
The long-term regulation of systemic arterial blood pressure is a topic beset with a remarkable degree of controversy. Some texts highlight the role of the kidney in setting arterial blood pressure, emphasizing its role in determining the volume of fluid in the circulation (Boron and Boulpaep, 2012; Mohrman and Heller, 2014). Sometimes these discordant viewpoints are presented one following another without resolution (Steddon et al, 2007). The confusion associated with this topic is important because extensive resources are directed toward the diagnosis and treatment of hypertension, since sustained elevation of arterial blood pressure. Given that the therapeutic activity of antihypertensive drugs is to a large extent empirical and may itself be associated with a variety of adverse effects, clear targeting of relevant tissue components in whatever organ system does regulate arterial pressure over long periods of time, would be highly desirable
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