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Endothelial cells play an important local regulatory role by secreting substances that control both vascular tone and structure1. The best characterized endothelium-derived relaxing factor (EDRF) is nitric oxide (NO)2,3, which is derived from the metabolism of L-Arginine4, by NO synthase (NOS)5, a constitutive enzyme present in endothelial cells.

Endothelium can deeply influence vascular tone and structure. The main endothelium derived factor is nitric oxide, which is not only a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell migration and proliferation, monocyte adhesion and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. In human hypertension, endothelial dysfunction has been documented in peripheral and coronary macro and microcirculation and in renal circulation. Impaired endothelium-dependent vasodilation associated with essential hypertension seems to be a primary phenomenon, since it can be detected in the offspring of essential hypertensive patients, shows no clear correlation with blood pressure value, and is not normalized by the mere reduction of blood pressure. The phenomenon responsible for endothelial alteration in essential hypertensive patients seems to be the activation of an alternative pathway involving cyclooxygenase which reduces NO availability through production of oxidative stress. This alteration in the NO pathway could be the main mechanism through which a dysfunctional endothelium could be a promoter of atherosclerosis and thrombosis in essential hypertension.

The usefulness of β-adrenoreceptor blocking agents in the treatment of hypertensive patients is now well known,1,2 but their mechanism(s) of action is not well established.2 Recently indomethacin, a potent inhibitor of prostaglandin (PG) synthesis,3,4 was found to reduce the hypotensive action of nonselective β-adrenoreceptor blocking agents in rats,5 rabbits,6 and humans.7–9 On this basis it has been proposed that an enhanced formation of prostaglandins may contribute to the hypotensive effect of these drugs, and this hypothesis has now received further support by the finding that propranolol increases the net production of PGE2 in the rat mesentery.10 Since, to our knowledge, no report exists showing that such a mechanism may be operative during treatment with cardioselective β-adrenoreceptor blocking agents, we decided to study this possibility in patients with uncomplicated essential hypertension treated with atenolol, a well-known cardioselective β-blocker.11

A circulating Na/K ATPase(sodium pump) inhibiting factor might cause hypertension in man. Furthermore, more recent evidence suggests that suppressed peripheral PRA values might be a marker for the presence of that factor in human hypertension(for a review see 1). We designed this study to further assess that possibility. Our specific aims were to evaluate whether biochemical or functional indices of Na/K ATPase inhibition are present in low renin human hypertension, either in primary aldosteronism (PA)or in the so called low renin essential hypertension(LREH). As controls, normal renin essential hypertensives(NREH) were taken.

It is still controversial whether the reduction of Na as well as the increase of K intake in hypertensive patients can reduce blood pressure (1,2,3,4), and the mechanisms which account for blood pressure decrease following a low Na intake are still debated. Aim of the study was to assess the efficacy of a K-rich/Na-poor salt (NaCl 50%, KCl 25%, K3C6H5O6 15%) in lowering blood pressure levels.