Sympatho-adrenal mechanisms and the antihypertensive response to thiazide diuretics

Thiazide diuretics lower the blood pressure during long-term treatment by reducing the peripheral vascular resistance. This seems to be related to the natriuresis rather than to a direct vasodilating effect of the thiazides. There is evidence that the volume depletion caused by thiazide treatment initially triggers an increase in sympathetic nerve activity, which may account for initial increases in vascular resistance. Although both responses subside during long-term treatment, there is no evidence showing a causal relationship between these changes. The long-term hemodynamic adaptation to thiazide treatment may be related to altered cardiovascular reflexes. Changes in sympathetic nerve activity and reduced vascular sensitivity to noradrenaline may contribute to the adaptation. An analysis of the relative importance of these mechanisms requires further studies comparing the time courses for various effects in responders and non-responders to the treatment.