Figure 201

Neuroendocrine pathways that are activated when vasodilators decrease blood pressure. These pathways lead ultimately to an increase in blood pressure and thus compromise the effectiveness of the vasodilators. The effectiveness can be preserved by coadminstration of propranolol (P) and a diuretic (D).

to an increase in heart rate and cardiac output. Large increases in cardiac output occurring as a result of vasodilator therapy will substantially counter the drug-induced reduction of blood pressure. Increased reflex sympathetic input to the heart also augments myocardial oxygen demand; this is especially serious in patients with coronary insufficiency and little cardiac reserve.

Plasma renin activity is elevated after treatment with vasodilators. The hyperreninemia appears to be due in part to enhanced sympathetic nervous activity. Elevated renin levels lead to an increase in the concentration of circulating angiotensin, a potent vasoconstrictor (see Chapter 18) and thus an increase in peripheral vascular resistance.

Thus, it seems that the lack of sympathetic nervous system inhibition produced by the vasodilators, which is advantageous in some ways, can also be a disadvantage in that reflex increases in sympathetic nerve activity will lead to hemodynamic changes that reduce the effectiveness of the drugs. Therefore, the vasodilators are generally inadequate as the sole therapy for hypertension. However, many of the factors that limit the usefulness of the vasodilators can be obviated when they are administered in combination with a (3-adrenoceptor antagonist, such as propranolol, and a diuretic. Propranolol reduces the cardiac stimulation that occurs in response to increases in sympathetic nervous activity, and the large increase in cardiac output caused by the vasodilators will be reduced. Propranolol also reduces plasma renin levels, and that is an additional benefit. The reduction in Na+ excretion and the increase in plasma volume that occurs with vasodilator therapy can be reduced by concomitant treatment with a diuretic. These relationships are shown in Fig. 20.1.

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