Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances.

Abstract

We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KC1 (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. EndotheHum-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endotheliuni and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I,, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KC1, serotonin, and prostaglandin F^ were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I 2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage. (Stroke 1989;20:657-663) P rolonged cerebral vasospasm frequently threatens the life of patients with subarachnoid hemorrhage following ruptured cerebral aneurysms. Despite extensive, long efforts, the pathogenesis of cerebral vasospasm is still controversial. It has been generally accepted that constituents of erythrocytes and substances produced during hemolysis of subarachnoid blood clots are related to the subsequent arterial narrowing.l2 Among the erythrocyte breakdown products, oxyhemoglobin (oxyHb) is considered to be a key substance in the genesis of cerebral vasospasm because of its vasoconstrictor activity in cerebral arteries 34 and its inhibitory effect on endothelium-dependent vasodilations. 56Since the vascular tone is controlled by vasoconstrictor and vasodilator interventions, cerebroarterial spasm is attributed possibly to an increased contractility and a decreased relaxation potential. Address for correspondence: Noboru Toda, Department of Pharmacology, Shiga University of Medical Sciences, Seta, Ohtsu 520-21, Japan.Received September 8, 1988; accepted October 12, 1988. Thus, it seems worthwhile to systematically evaluate the effect of oxyHb on contraction and relaxation responses of cerebral arteries. Articles published so far include results relating to the acute effects of erythrocyte breakdown products. 5 " 9 After subarachnoid hemorrhage, cerebral arteries are surrounded by blood constituents for a long time, until the spasm is evoked. The...

Cerebral Artery Remodeling in Rodent Models of Subarachnoid Hemorrhage

“…It was not the purpose of this study to investigate the nature of possible blood-derived factors causing tone and subsequent structural changes in the vascular wall. Several contractile factors have been identified [27] and fresh serum and platelet-rich plasma are known to contain agents that cause temporary vasoconstriction [25,28]. However, irrespective of the exact mechanism causing contraction, we believe that the remodeling that is associated with blood exposure is a consequence of sustained contraction, in line with previous work where we showed that persistent contraction induces inward remodeling [5,6,29,30,31].…”

“…We additionally tested whether transglutaminase inhibition prevents these changes. In the current in vitro experiments, blood induced active tension development, in accordance with previous studies [25,26]. It was not the purpose of this study to investigate the nature of possible blood-derived factors causing tone and subsequent structural changes in the vascular wall.…”

“…4). The 3-day time point was based on available data regarding the development of vasospasm [1,23,24,25]. Subsequently, animals were sacrificed and vessels were harvested.…”

Endothelial injury following experimental subarachnoid hemorrhage in rats: Effects on brain blood flow

“…Other clinical studies have demonstrated an increased elevation in endothelin levels in the cerebrospinal fluid of patients suffering from SAH (Willette and Sauermelch, 1990;Fujimori et al, 1990). Furthermore, EDRF is reported to be impaired in experimental models of SAH (Lye et al, 1982;Onoue et al, 1989).…”

The effect of hemoglobin on vasodilatory effect of calcium antagonists in the isolated rabbit basilar artery

“…Onoue, et aL, 23 investigated the effect of prolonged exposure of canine cerebral arterial segments to oxyhemoglobin, and reported impaired activity of the electrogenic sodium pump. This may also alter the regulation of intracellular Ca ++ concentration mediated by both membrane polarization and the Ca ++ extrusion mechanism?…”