The effect of nitric oxide inhibition on blood pressure depends on rat strain

Nitric oxide is a continuously released endothelium-derived vasodilator and plays an important role in the maintenance of blood pressure (BP). Rat strains appear to differ in their resting BP and their response to the intravenous administration of N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor. The presence of diabetes and hypertension also leads to differences in BP responses to l-NAME. We postulated that the contribution of NO to resting BP varies between rat strains and certain strains may be more sensitive to the effects of NO blockade.

Blood pressure was continuously measured using a carotid arterial catheter and the responses to l-NAME were compared in anesthetized Lewis and Sprague-Dawley rats during a 2-h control period and a 2-h experimental period. l-NAME was given by a 50 mg/kg bolus followed by a 10 mg/kg/h infusion via a mesenteric vein.

During the control period, the Lewis animals had lower systolic and diastolic BPs of 103 +/- 1 and 80 +/- 1 mm Hg compared with 127 +/- 1 and 105 +/- 1 mm Hg measured in Sprague-Dawley rats (P < 0.01). Although l-NAME infusion increased systolic BP in both strains compared with control values (P < 0.00005), the magnitude was significantly greater in Sprague-Dawley than Lewis animals (P = 0.0142); additionally, the BP was unstable in the Lewis animals. Furthermore, pulse pressure decreased during l-NAME in Lewis animals but increased in Sprague-Dawley animals (P < 0.00005). There were no significant changes in serum concentrations of aspartate transaminase nor of nitrite plus nitrate after l-NAME in either group.

These results indicate that the effect of l-NAME on systemic BP differs markedly in Sprague-Dawley and Lewis rats, suggesting that the role of nitric oxide in regulation of resting vascular resistance may differ significantly between these rat strains. Rat strain is an important consideration for valid comparisons between studies.