Mechanism of the Altered Blood Pressure Responsiveness Produced by Chlorothiazide *

How do thiazide and thiazide-like diuretics lower blood pressure?

“…[71][72][73][74][75] These data are difficult to interpret, since they could be due to a non-specific depressant effect of volume depletion and, in one study, responsiveness to noradrenaline was restored by re-expansion of plasma volume with dextran. 72 Local intra-arterial infusion of thiazides provides better evidence for direct vasodilator actions in vivo. Infusion of chlorothiazide into the femoral artery of dogs inhibited vasoconstrictor responses resulting from stimulation of the lumbar sympathetic nerves, without affecting the response to adrenaline.…”

Reduced Vascular Response to Angiotensin Ii in Secondary Hyperaldosteronism*

“…Friedman and Allardyce (25) also showed the importance of ionic distribution, particularly of sodium, in the maintenance of tension in artery segments. Chlorothiazide 4 has been shown to modify the pressor response to infused l-norepinephrine (26)(27)(28), and dogs given prior treatment with 3,4-dihydrochlorothiazide 5 have a diminished pressor response to angiotensin (29). These were all acute experiments.…”

“…These were all acute experiments. The initial hypotensive action of chlorothiazide may be due to a fall in blood volume and is partially reversed by plasma expansion (27). The blood volume returns to normal, however, after several weeks (30), while a hypotensive action persists.…”

Role of beta-adrenergic receptor blocking agents in hypertensive diseases: personal thoughts as the controversy persists

“…Moreover, as arterial pressure became reduced, heart rate and ventricular contractility also decreased along with the so-called 'double product' and myocardial oxygen consumption thereby providing a more sophisticated rationale for the use of these agents in patients with coronary arterial disease, angina pectoris as well as in hypertension. As a corollary to this hemodynamic concept, let us remember that we still are unable to provide an adequate hemodynamic explanation for the hypotensive action of the diuretic agents when used in hypertension [Frohlich, 1987;Freis et al 1960;Frohlich et al 1960]. These issues then, were one of our first hemodynamic and clinical pharmacological lessons that antihypertensive therapy is neither simple nor straightforward.…”