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Clinical and therapeutic implications of new peptides in hypertension

Two angiotensin receptor subtypes have been identified using specific ligands. The AT1 receptor mediates the known actions of angiotensin, but no function has yet been ascribed to the AT2 receptor. Inhibition of atrial natriuretic peptide metabolism by neutral endopeptidase inhibitors enhanced circulating levels of atrial natriuretic peptide and increased urinary sodium excretion in heart failure patients. In spontaneously hypertensive rats, chronic neutral endopeptidase 24.11 inhibition lowered arterial blood pressure. Transgenic mice, expressing atrial natriuretic peptide at very high levels, differ from normal mice in having a lower mean arterial blood pressure and enhanced ability to excrete a sodium load. Phosphoramidon, a metalloneutral endopeptidase inhibitor, blocks in vitro and in vivo conversion of proendothelin to the mature hormone and lowers blood pressure in spontaneously hypertensive rats. Patients with an endothelin-secreting tumor were hypertensive, and removal of the tumor restored pressure to normal. Regrowth of the tumor resulted in the return of hypertension. Endothelin may contribute to several important pathologic conditions including hypertension, ischemic heart disease and myocardial infarction, and renal failure.