A novel vasopressin peptide lowers blood pressure through decreases in cardiac output

The changes in blood pressure, cardiac output, and total. peripheral conductance evoked by the novel hypotensive arginine vasopressin (AVP) - like peptide, d(CH2)(5)[D-Tyr(Et)(2) Arg(3),Val(4),Arg(7),Eda(9)]AVP (HYPO-AVP), were recorded in conscious unrestrained Sprague-Dawley rats implanted with radiotelemetry pressure transducers and ultrasonic transit-time flowprobes. Intravenous infusions of 0.6, 1.0, 2.0, and 4.0 mug.kg(-1).min(-1) of HYPO-AVP evoked dose-related decreases in blood pressure. At the lowest dose of 0.6 mug.kg(-1).min(-1), the fall in blood pressure was associated with a small but significant increase in total peripheral conductance. Cardiac output was unchanged. In contrast, at the three higher doses of 1.0, 2.0, and 4.0 mug.kg(-1).min(-1), the fall in blood pressure was related to a dramatic fall in cardiac output. Indeed, total peripheral conductance decreased, preventing blood pressure from falling further. These hemodynamic findings should help to direct future research into the mechanism of the putative hypotensive property of vasopressin, a property that attenuates the well established blood pressure elevating actions of the peptide.