Acute effects of nitric oxide blockade with L ‐NAME on arterial haemodynamics in the rat

1 We employed the technique of impedance spectral analysis to investigate the role of endogenous nitric oxide (NO) in the regulation of steady 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 aortic flow wave with an electromagnetic flow probe. The pressure and flow waves were subjected to Fourier transform for the analysis of impedance spectra. 3 The baseline cardiovascular parameters were mean arterial pressure (APm) 95±9 mmHg, heart rate (HR) 338±9 b.p.m., stroke volume (SV) 0.23±0.01 ml, cardiac output (CO) 77.8±1.6 ml min −1 , total peripheral resistance (TPR) 98±11 (×10 3 ) dyne  s  cm −5 , characteristic impedance ( Zc ) 2046±141 dyne  s  cm −5 , arterial compliance at mean AP (Cm) 3.78±0.22 μl mmHg −1 and backward pulse wave ( P b ) 12.9±0.6 mmHg. 4 An NO synthase inhibitor, N G ‐nitro‐ L ‐arginine monomethyl ester ( L ‐NAME) was administered at graded intravenous doses. This agent caused dose‐dependent increases in AP and TPR with decreases in HR. At an accumulative dose of 10 mg kg −1 , APm was increased by 29±3 mmHg (+31%) and TPR by 49±6 (×10 3 ) dyne  s  cm −5 (+50%), 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 Zc and P b were slightly increased by 14–15%. Cm was decreased by 1.09 μl mmHg −1 (−29%). L ‐NAME also did not significantly affect the ventricular work 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 result indicated that blockade of constitutive NOS, but not iNOS is involved 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 elevated. The pattern of haemodynamic changes was different from that following L ‐NAME. 7 The results suggest that blockade of the endogenous NO affects predominantly the arterial pressure and peripheral resistance. The Windkessel functions such as arterial impedance and pulse wave reflection are slightly increased. Ventricular works are not significantly altered.British Journal of Pharmacology (1997) 122 , 1237–1243; doi: 10.1038/sj.bjp.0701496