ACUTE EFFECTS OF NITRIC-OXIDE BLOCKADE WITH L-NAME ON ARTERIAL HEMODYNAMICS IN THE RAT

1 We employed the technique of impedance spectral analysis to investig ate the role of endogenous nitric oxide (NO) in the regulation of stea dy and pulsatile haemodynamics in Wistar Kyoto rat (WKY). 2 A total of 12 WKYs was anaesthetized with pentobarbitol sodium (40 mg kg(-1), i. p.) and artificially ventilated with an animal respirator. The aortic pressure wave was monitored with a high fidelity Millar sensor, and ao rtic flow wave with an electromagnetic flow probe. The pressure and fl ow waves were subjected to Fourier transform for the analysis of imped ance spectra. 3 The baseline cardiovascular parameters were mean arter ial pressure (APm) 95+/-9 mmHg, heart rate (HR) 338+/-9 b.p.m., stroke volume (SV) 0.23+/-0.01 mi, cardiac output (GO) 77.8+/-1.6 mi min(-1) , total peripheral resistance (TPR) 98+/-11 (x10(3)) dyne s cm(-5), ch aracteristic impedance (Zc) 2046+/-141 dyne s cm(-5), arterial complia nce at mean AP (Cm) 3.78+/-0.22 mu l mmHg(-1) and backward pulse wave (P-b) 12.9+/-0.6 mmHg. 4 An NO synthase inhibitor, N-G-nitro-L-arginin e monomethyl ester (L-NAME) was administered at graded intravenous dos es. This agent caused dose-dependent increases in AP and TPR with decr eases in HR. At an accumulative dose of 10 mg kg(-1), APm was increase d by 29 +/- 3 mmHg (+31%) and TPR by 49+/-6 (x10(3)) dyne s cm(-5) (+5 0%), while HR was reduced by 37+/-5 b.p.m. (-11%) and CO by 10.4+/-0.8 ml min(-1) (-14%). The pulsatile haemodynamics including Ze and P-b w ere slightly increased by 14-15%. Cm was decreased by 1.09 mu l mmHg(- 1) (-29%). L-NAME also did not significantly affect the ventricular wo rk including the steady, oscillatory and total work. 5 Aminoguanidine, a specific inhibitor for inducible NO synthase (iNOS), in dose 10-60 mg kg(-1) i.v. did not alter the AP, HR and other parameters. The resu lt indicated that blockade of constitutive NOS, but not iNOS is involv ed in these changes. 6 Angiotensin II (Ang) in various infusion doses was used to produce a profile of AP increase similar to that caused by L-NAME. Ang remarkably increased Zc, while TPR was moderately elevate d. The pattern of haemodynamic changes was different from that followi ng L-NAME. 7 The results suggest that blockade of the endogenous NO af fects predominantly the arterial pressure and peripheral resistance. T he Windkessel functions such as arterial impedance and pulse wave refl ection are slightly increased. Ventricular works are not significantly altered.