Characterization of acute hemodynamic effects of antidiuretic agonists in conscious dogs

Conscious dogs instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter) received intravenous injections of 4-valine-8-D-arginine vasopressin (VDAVP) and 1-deamino-8-D-arginine vasopressin (dDAVP), two specific antidiuretic agonists. Both agents led within minutes to dose-dependent increases in cardiac output and heart rate, as well as to decreases of total peripheral resistance and mean arterial pressure. Indomethacin did not affect the hemodynamic responses to VDAVP administration. The analog 8-arginine-9-desglycinamide vasopressin, which retains behavioral effects of vasopressin but is a weak antidiuretic agonist, showed only weak hemodynamic effects that were similar in nature to those of VDAVP and dDAVP. Thus, the capability to increase cardiac output and decrease peripheral resistance appeared to correlate best with the antidiuretic activity of the three vasopressin analogs tested. We also observed that pretreatment of dogs with a combined vasopressor (V1) and antidiuretic (V2) vasopressin antagonist completely prevented the increase in cardiac output that is normally associated with the infusion of arginine-vasopressin, 10 ng kg-1 min-1, after V1 blockade. Our results confirm the existence of powerful, dose-related hemodynamic effects of various antidiuretic agonists in conscious dogs; these effects being opposite to those normally elicited by arginine-vasopressin.