Effects of NG‐nitro‐l‐arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin‐releasing hormone

Abstract

1. The effects of 300 mg kg-1 of the nitric oxide (NO) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the regional blood flow, on the flow response to 1 mg kg-1 of thyrotropin-releasing hormone (TRH) and on cerebral blood flow autoregulation were studied in urethane anesthetized rabbits subjected to unilateral sectioning of the cervical sympathetic claim. The blood flow measurements were performed by the tracer microspheres method. 2. The cerebral arteriovenous difference in oxygen saturation (CAVOD) was measured before and after the administration of L-NAME and TRH in order to ascertain whether the effects on cerebral blood flow that were observed were secondary to changes in cerebral metabolism. 3. L-NAME caused a significant decrease in blood flow in several cerebral regions; CBFtot decreased to 72 +/- 4% of control (P < 0.001). An increase in blood pressure and a concurrent decrease in heart rate and cardiac output were noted. 4. In the eye, L-NAME caused a reduction in uveal blood flow which was more pronounced on the sympathetically intact side; in the retina the blood flow decreased to 50% of control on both sides. 5. The administration of TRH in animals pretreated with L-NAME caused a significant increase in blood pressure and cerebral blood flow. 6. In L-NAME-treated animals the CBF was not affected when the mean arterial blood pressure was increased by ligation of the abdominal aorta. 7. The CAVOD increased from 56.0 +/- 5.2 to 73.6 +/- 3.5%, 20 min after the administration of L-NAME. In animals given 1 mg kg-1 TRH after L-NAME the CAVOD decreased to 54.6 +/- 4.6%, 5 min after the injection of TRH.8. The results of the present study indicate that endogenous NO is involved in the regulation of regional blood flow and blood pressure in the anaesthetized rabbit. The reduction in cerebral blood flow that was caused by L-NAME was not due to a reduction in cerebral metabolism. An interaction between the NO synthesis/release/effect and the sympathetic nervous system was found in the uvea. There was no evidence for a major involvement of NO in the cardiovascular responses to TRH and autoregulation of cerebral blood flow was not abolished by L-NAME.