A comparison between haemodynamic effects of vasopressin analogues.

Some analogues of arginine vasopressin (AVP) reportedly possess hypotensive properties, and two such peptides are Cys(1)-Tyr(2)-Phe(3)-Val(4)-Asn(5)-Cys(6)-Pro(7)- d-Arg(8)-Gly(9)-NH(2) (VD-AVP) and d(CH(2))(5)-Cys(1)- d-Tyr(Et)(2)-Arg(3)-Val(4)-Asn(5)-Cys(6)-Lys(7)-Lys(8)-ethylenediamine(9) (TA-LVP). In the present investigation we examined the effects of TA-LVP (0.3, 1.0 and 3.0 microg/kg/min), VD-AVP (0.3, 1.0 and 3.0 microg/kg/min) and AVP (1.0, 3.0, 10 ng/kg/min) on haemodynamics, blood volume (BV) and plasma troponin levels in anaesthetised rats. Infusion of TA-LVP significantly ( P<0.05) reduced blood pressure (-45+/-3%; n=8; mean +/- SEM), mean circulatory filling pressure ( P(mcf); -41+/-3%), and cardiac output (CO; -59+/-4%). The reduction in CO at a lower dose of TA-LVP was due to reduced venous tone, while at higher doses the reduction was predominantly the result of reduced BV (-35+/-4%). The large decrease in BV during the infusion of TA-LVP, substantially increased resistance to venous return (50+/-11%), which was the main contributor in reducing CO. Administration of AVP significantly increased blood pressure (41+/-4%) and arterial resistance (98+/-16%) without any impact on P(mcf) and BV, while significantly reducing CO (-26+/-5%). Infusion of VD-AVP did not produce hypotension, but produced a modest but significant reduction in CO (-18+/-5%) and insignificant but moderate increases in peripheral resistance (30+/-12%) and resistance to venous return (28+/-8%). Plasma troponin levels were not affected by any of the peptides. The hypotensive action of TA-LVP was due to a reduction in CO as a result of a reduced pre-load, while the pressor effect of AVP increased after-load sufficiently to impede flow, reducing CO. VD-AVP was devoid of any hypotensive effects, suggesting that V(2)-vasopressin receptors are most likely to play a limited role in the control of cardiac and vascular function in these animals.