Abstract
Some analogues of arginine vasopressin (AVP) reportedly possess hypotensive properties, and two such peptides are Cys1-Tyr2-Phe3-Val4-Asn5-Cys6-Pro7-d-Arg8-Gly9-NH2 (VD-AVP) and d(CH2)5-Cys1-d-Tyr(Et)2-Arg3-Val4-Asn5-Cys6-Lys7-Lys8-ethylenediamine9 (TA-LVP). In the present investigation we examined the effects of TA-LVP (0.3, 1.0 and 3.0 μg/kg/min), VD-AVP (0.3, 1.0 and 3.0 μg/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 (Pmcf; −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 Pmcf 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 V2-vasopressin receptors are most likely to play a limited role in the control of cardiac and vascular function in these animals.
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This work was supported by a grant-in-aid from the Heart and Stroke Foundation of New Brunswick. These experiments conform to Canadian Council on Animal Care (CCAC) guidelines.
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Tabrizchi, R., Ford, C.A. A comparison between haemodynamic effects of vasopressin analogues. Naunyn-Schmiedeberg's Arch Pharmacol 370, 340–346 (2004). https://doi.org/10.1007/s00210-004-0986-6
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DOI: https://doi.org/10.1007/s00210-004-0986-6