Hemolysate Inhibits Cerebral Artery Relaxation

Abstract

Summary: In helical strips of dog middle cerebral arteries partially contracted with prostaglandin (PG) F2a, relax ations induced by angiotensin-II, possibly mediated by PGI2, and those induced by PGH2 were reversed to a contraction or markedly reduced by treatment with he molysate, which, however, attenuated the PGIz-induced relaxation only slightly. The relaxant response of human middle cerebral arterial strips to PGHz was also sup pressed by hemolysate. Dog and monkey middle cerebral arteries responded to transmural electrical stimulation and nicotine with transient relaxations, which were quite susceptible to tetrodotoxin and hexamethonium, respec tively; the relaxations were abolished almost completely by hemolysate and methylene blue. On the other hand, the relaxant response of dog cerebral arteries to a low concentration of K + was not influenced by hemolysate or by methylene blue, but was reversed to a contraction by treatment with ouabain. Relaxations induced by subProlonged cerebral vasospasm after subarach noid hemorrhage evokes severe impairment of local cerebral blood flow, frequently resulting in fatal brain dysfunction. Constituents of erythrocytes and substances produced during the course of hemo lysis of a blood clot appear to play an important role in the genesis of cerebral vasospasm (White, 1983a,b), as injections of autologous blood into ce rebral subarachnoid space provokes angiographic ally verified vasospasm in monkeys, dogs, and rats (Allen and Bahr, 1979; Barry et aI., 1979; Ritchie et aI., 1980), and hemolysate applied in vitro and in situ intensively contracts large cerebral arteries (Osaka, 1977; Ozaki and Mullan, 1979; Toda et aI., 1980). Such an arterial smooth muscle contraction is hypothesized to be associated with vasocon strictor prostaglandins (PGs) liberated from the 46stance-P and nitroglycerin were markedly inhibited by hemolysate; removal of endothelium abolished the relax ation by substance-P, but did not influence the nitroglyc erin-induced relaxation. Hemolysate may interfere with the biosynthesis of PGI2 in the vascular wall, thereby re versing the relaxation induced by angiotensin-II and PGH2 to a contraction. Relaxations induced by electrical and chemical stimulation of vasodilator nerves inner vating cerebral arteries appear to be elicited by a mecha nism dependent on cellular cyclic guanosine monophos phate (GMP), like that underlying the substance-P-in duced and nitroglycerin-induced relaxation. These actions of hemolysate may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage. Key Words: Cerebral artery relaxation-Erythrocyte break down products-Prostacyclin-Prostaglandin H2-Va sodilator nerve.

Neurotransmission in the Sheep Middle Cerebral Artery: Modulation of Responses by 5-HT and Haemolysate

“…Similar results have also been re ported in the middle cerebral arteries of the dog and monkey; however, the influence of the endothelium in these studies was not determined Toda, 1988). Endothelium-derived relaxant factor(s) (EDRF), released by agonists such as ace tylcholine, are known to be inhibited by oxyhaemo globin, which has been shown to be present in high quantities in haemolysate Martin et al, 1985).…”

“…It has been suggested that haemolysate can also inhibit prostacyclin production (Toda, 1988); how ever the addition of indomethacin had no effect on the TNS response. When whole blood is incubated at 37°C, the levels of oxyhaemoglobin increase with time up to 14 days, probably due to the breakdown of erythrocytes, which closely parallels the time course of cerebral vasospasm (Duff et aI., 1987).…”

“…This suggests that 5-HT released from aggregating platelets may be taken up by the noradrenergic nerves and subse quently released, causing spasm. There is also some evidence that haemolysate, which inhibits the ef fects of endothelium-derived relaxing factor (EDRF) (Martin et aI., 1985), can block relaxations induced by transmural stimulation of other cerebral arteries (Lee et aI., 1984;Toda, 1988).…”

No effect of angiotensin II AT2-receptor antagonist PD 123319 on cerebral blood flow autoregulation

“…19 Ang II-mediated vasodilation has been found in rat brain arterioles 20,21 and in dog middle cerebral arteries. 22 Ang II-mediated vasoconstriction has been reported in cat middle cerebral artery strips. 23 This dual effect of Ang II suggests stimulation of two types of Ang II receptors in the ACE-I shift the limits of CBF autoregulation towards lower BP.…”

Molecular biological considerations in cerebral vasospasm following aneurysmal subarachnoid hemorrhage

“…[66,67] Oxyhemoglobin is also known to inactivate NO by directly binding to its heme moiety. [6,17,20,25,32,44,72,73] This phenomenon could explain the finding by some investigators that levels of soluble guanylate cyclase are inappropriately low in CDCV, [35] thus the failure of intrinsic vasodilatory responses to compensate for arterial narrowing. The time course of clinical CDCV is consistent with the delayed and persistent rise in oxyhemoglobin levels that accompany RBC lysis.…”