Effects of N^G‐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-' 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-' of thyrotropin-releasing hormone (TRH) and on cerebral blood flow autoregulation were studied in urethane anaesthetized rabbits subjected to unilateral sectioning of the cervical sympathetic chain. 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; CBF,O, 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-' 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.

Inhibition of nitric oxide biosynthesis and carotid arteriovenous anastomotic shunting in the pig

“…However, it may be noted that under pentobarbitone anaesthesia, capillary blood flow is approximately one-third of the total carotid blood flow (Saxena & Verdouw, 1982;1985;Den Boer et al, 1992;present results) and thus the basal release of NO may already be too low to detect a significant decrease. In contrast to a number of studies which reported a moderate reduction in cerebral blood flow following NOsynthase inhibition, suggesting a basal NO-release in this part of the cranial circulation (Kovaich et al, 1992;Prado et al, 1992;Seligsohn & Bill, 1993), in our present experiments L-NAME failed to reduce the cerebral component of carotid blood flow. The absence of an endothelial NO-dependent dilator tone is supported by the recent finding that cultured rat brain microvessel endothelial cells do not show basal release of NO (Durieu-Trautmann et al, 1993).…”

“…Gardiner et al, 1990;Van Gelderen et al, 1991). In doses up to 30 mg kg-', both L-NAME and N0-nitro-Larginine (L-NOARG) are without effect on brain blood flow (Van Gelderen et al, 1991;Faraci & Heistad, 1992), though in higher doses these agents can significantly reduce cerebral blood flow (Kovach et al, 1992;Prado et al, 1992;Seligsohn & Bill, 1993). It is tempting to speculate that at high doses NO-synthase inhibitors may act at a different site within the brain.…”

Dominant role of an endothelium‐derived hyperpolarizing factor (EDHF)‐like vasodilator in the ciliary vascular bed of the bovine isolated perfused eye

“…There is now compelling evidence to support the view that endothelium-derived nitric oxide is an important mediator of vasomotor tone in the eye (for review see Koss, 1999). For example, inhibition of nitric oxide synthase in vivo in a wide range of species reduces basal ocular blood¯ow, as measured using radiolabelled microspheres (Nilsson, 1996;Hardy et al, 1996;Seligsohn & Anders, 2000) or laser Doppler¯owmetry (Zagvazdin et al, 1996;Koss, 1998;Luksch et al, 2000). It remains to be determined whether this tonic vasodilator in¯uence of nitric oxide on the ocular vasculature in vivo is derived from the endothelium as a result of basal release or release stimulated by agonists (Benedito et al, 1991a;Gidday & Zhu, 1995) or by¯ow (Rubanyi et al, 1986), or is derived from perivascular nitrergic nerves (Nilsson, 1996;Toda et al, 1998;Zagvazdin et al, 1996).…”

The role of nitric oxide in hyperaemic response to flicker in the retina and optic nerve in cats

“…In rabbits, a high dose of L-NAME has been shown to induce a marked reduction in blood flow in the retinal blood vessels (Seligsohn et al 1993). These blood vessels are restricted to the myelinated fiber layer of the retina and can therefore be regarded as an extension of the optic nerve into the eye.…”

“…The observation that inhibitors of NO formation cause intraocular vasoconstriction following either intravenous (Granstam et al 1993;Mann et al 1995;Seligsohn & Bill 1993;Vogel et al 1994) or local (Donati et al 1994;Meyer et al 1993) administration indicates that, in fact, N O is normally released in the eye. As in many other tissues, NO release from the endothelial cells of the blood vessels is expected (Bergua 1995;Chakravarthy et al 1995).…”