The demonstration that exogenous atrial natriuretic polypeptide (ANP) has markedly lowered plasma antidiuretic hormone (ADH) suggests a possible negative control of endogenous ANP on the secretion of ADH from the posterior hypophysis. To test this possibility and to clarify the role of ADH and ANP in the pathophysiology of essential hypertension (EHT), the responses of ADH and ANP to a hypertonic saline infusion were investigated in EHT patients and normotensive subjects (NT). Twenty inpatients with EHT (10 males and 10 females; 50.5 +/- 6.5y) and 10 NT subjects (5 males and 5 females; 50.6 +/- 7.8y) underwent a 20 min intravenous infusion of hypertonic saline (2.5% NaCl; 0.25ml/kg/min) in a fasting state. Blood samples were drawn before and 10, 20, 30, 45 and 60 min after the infusion and analyzed for ADH and ANP as well as plasma osmolarity (Posm), Na and albumin. Basal levels of ADH and ANP were not significantly different between NT and EHT. ADH was rapidly increased by the infusion in both groups; however, its percent increase was much higher in EHT than in NT during and after the infusion. Surprisingly, a highly significant negative correlation between ADH and ANP was found before and after the infusion in both groups. Although blood pressure was not changed significantly, the enhanced response of ADH to a sodium and volume load may play a role in part in the pathophysiology of EHT. In addition, it has been suggested that a possible suppression by ANP on the secretion of ADH may be one of the mechanisms of the diuretic action of ANP.