Cardiovascular, adrenocorticotropin, and cortisol responses to hypertonic saline in euvolemic sheep are altered by prostaglandin synthase inhibition

Small volume intravenous infusions of hypertonic saline (HTS) increase blood pressure, heart rate, adrenocorticotropic hormone (ACTH), and cortisol by mechanisms that are not fully understood. We hypothesized that HIS infusions increase prostaglandin biosynthesis and that a prostaglandin synthase metabolite is responsible for mediating actions of HIS. We further hypothesized that thromboxane A(2) (TxA(2) is the specific metabolite responsible for mediating responses to HTS infusion. Adult female sheep (n = 8) were chronically instrumented with vascular catheters and infused intravenously with 7.5% saline at a rate of 4 mL.kg(-1) over 5 min with or without pretreatment with the prostaglandin synthase inhibitor flunixin. Blood pressure, ACTH, and cortisol increased in response to HTS, and these responses were prevented by flunixin. Heart rate increased in response to HTS infusion, and flunixin reduced but did not prevent a heart rate response. Hematocrit decreased significantly in response to HTS but only following flunixin treatment. Arginine vasopressin increased but only modestly in response to HTS, and responses were not different following flunixin. Arterial pH, partial pressure of CO2, and partial pressure of O-2 did not change. Circulating concentrations of thromboxane B-2, a stable metabolite of TxA(2) and an index of TxA(2) formation, remained low and did not change in response to HTS. We conclude that heart rate, blood pressure, ACTH, and cortisol responses to HTS are mediated at least in part by a product of prostaglandin synthase metabolism. These responses were not due to increases in circulating concentrations of TxA(2), but might involve local formation of TxA(2), or some other prostaglandin synthase metabolite.