Vasodilation by intrathecal lipopolysaccharide of the cerebral arteries after subarachnoid haemorrhage in dogs

Abstract

To investigate the influence of inducible nitric oxide synthase on cerebral arteries after subarachnoid haemorrhage (SAH) in vivo, lipopolysaccharide (LPS), a major inducer of inducible nitric oxide synthase, was injected intracisternally into control and SAH model dogs. Intracisternal injection of LPS (0.5 mg) produced a long-lasting, submaximal vasodilation of the basilar artery of control dogs on angiography. This effect became significant at 4 hours after LPS injection and plateaued after 6 hours. This vasodilation was reduced by N(G)-monomethyl-L-arginine. Vasopressin slightly suppressed the vasodilation, while bradykinin increased it. The concentration of L-arginine in CSF decreased after LPS injection, while that of L-citrulline increased. In cytokines, the concentration of tumour necrosis factor-alpha; (TNF-alpha;) in CSF increased transiently at 4 hours after LPS injection, while interleukin-1 beta, interleukin-6, interferon-gamma, did not change. These data suggest that vasodilation by LPS is mainly due to nitric oxide predominantly synthesized by an inducible nitric oxide synthase, proximally induced by TNF-alpha. Our data make it unlikely that SAH itself induces the inducible nitric oxide synthase in vascular tissue, since isolated endothelium-denuded basilar artery from SAH model dogs did not respond to L-arginine. In SAH model dogs, the degree of vasodilation by LPS differed with the severity of vasospasm. Vasodilation was much greater in mild than in severe vasospasm in dogs, and was increased by superoxide dismutase. These findings suggest that the induction of inducible nitric oxide synthase or its activity may be less effective in severe vasospasm.

Inducible nitric oxide synthase: a possible key factor in the pathogenesis of chronic vasospasm after experimental subarachnoid hemorrhage

“…Regarding the importance of NO, most recent reports postulate decreased levels of endothelial NO or decreased efficacy of this mediator as the main cause of vasospasm. 3,24,25,29,33,48,57,69,75 In general these results were drawn on the basis of the effect of NO agonists and antagonists in experimental vasospasm. There is little information on direct assessments of cNOS and iNOS levels after SAH.…”

“…Both reports address the physiological vascular tone-modulating cNOS. The iNOS isoform has been neglected until recently, when Tanazawa, et al, 69 suspected that induction of iNOS might be an important factor after SAH in counteracting vasospasm. These authors provided indirect evidence that induction of iNOS may be less effective in dogs exhibiting severe vasospasm after experimental SAH.…”

“…74 This isoform is induced by various inflammatory factors such as cytokines, lipopolysaccharides, hemoglobin breakdown products, and endotoxins. 1,8,11,14,20,22,23,34,40,47,59,64,65,69,71,76 The properties of both constitutively expressed NOS isoforms, such as maintaining adequate tissue perfusion, 13,27 are better known than the characteristics of the iNOS isoform. Endothelial NO overproduction would be expected as a physiological response to counteract vasospasm.…”

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

“…A recent study showed that PGE 2 could be produced by microvessel endothelial cells in culture, probably through COX2 induction, after exposure to TNF-a (93). There is evidence of early increased TNF-a concentration in the CSF (91,94). A final point is that in large cerebral arteries PGE2 has been shown to induce contraction (95).…”

Neurogenic factors in renal hypertension

“…Complex relationships exist between the SNS, NO, and cytokines [46][47][48][49][50][51][52]. One possible mediator for the increase in NO expression is interleukin-1β (IL-1β).…”