Dose-dependant effects of ace-inhibition on the cardiovascular actions of human ‘new pressor protein’ (NPP) related to βfxIIA

Abstract

The blood pressure, heart rate and catecholamine releasing effects of NPP are potentiated by ACE-inhibition with Captopril (CAP) (J Hypertens: 16: 311, 1998; Can J Cardiol 18:.1077-1086, 1093-1103, 2002. We therefore examined how NPP's actions are influenced by different doses of CAP. NPP was given (20 μL plasma equivalent) to anesthetized (Inactin) male, Wistar bioassay rats (250-350g) divided into 4 groups, each n=6. These were control (no CAP) & CAP at 0.33, 2.5, or 10 mg/kg, i.v. Systolic and diastolic blood pressures (SBP & DBP) and heart rate (HR) were recorded using a Maclab/8 PowerMac 7200 computer system and plasma samples taken to determine adrenaline (ADR), noradrenaline (NA) and dopamine (DA) in response to NPP before/after adminstering CAP. Increasing doses of CAP produced marked increments in most of the measured responses, especially HR & plasma ADR. The profound increases in ADR after CAP supports our findings that NPP somehow triggers the sympatho-adrenal system. We postulate that NPP's effects are mediated by peptides and that the potentiating effects of CAP may result from prolonged, intensified actions of peptide(s) preserved by ACE inhibition. Bradykinin is one such candidate mediator whose endogenous production can be related to FXII activation in the body but its postulated participation in a hypertensive effect requires explanation. NPP/βFXIIa may represent a new axis for blood pressure regulation that links coagulation FXII with the sympatho-adrenal system. Supported by HSFO grants NA3478, T4136 (See Table) Δ: peak increments over corresponding control baseline values after injecting NPP; Means ± SEM, p<0.05 vs. no CAP; p<0.05 vs. CAP 0.33; p<0.05 vs. CAP 2.5 Δ: peak increments over corresponding control baseline values after injecting NPP; Means ± SEM, p<0.05 vs. no CAP; p<0.05 vs. CAP 0.33; p<0.05 vs. CAP 2.5