Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries.

Abstract

We compared responses to calcium ionophore A23187, vasopressin, and substance P in helical strips of dog middle cerebral, basilar, and posterior communicating arteries to obtain a better understanding of humoral control of cerebrovascular tone in different brain regions and its potential impact on mechanisms of cerebral vasospasm. A23187 relaxed these different arterial strips partially precontracted with prostaglandin F 2a to a similar extent. Vasopressin produced concentration-dependent relaxation in basilar and posterior communicating arterial strips, whereas middle cerebral arterial strips either contracted or relaxed slightly. Relaxations induced by A23187 and vasopressin were either abolished or converted to contractions by removal of the endothelium. In contrast, the relaxation of cerebral arterial strips to substance P was markedly attenuated but not abolished by endothelium denudation; the remaining relaxation was suppressed by indomethacin. In some cerebral arterial strips with intact endothelium, substance P caused a transient contraction that was reversed to a relaxation by indomethacin or ONO-3708, a prostaglandin antagonist. In arterial strips denuded of endothelium from the same dogs, substance P always produced relaxations. Relaxations of cerebral arterial strips to A23187 and vasopressin appear to be mediated by endothelium-derived relaxing factor. The function of vasopressin receptors in endothelial cells differs markedly in basilar and posterior communicating arteries versus middle cerebral arteries. Substance P-induced relaxations appear to be primarily associated with endothelium-derived relaxing factor and with prostaglandin I 2 , whereas contractions appear to be mediated by endotheliumderived prostaglandins. (Stroke 1988;19:1388-1394)

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

“…33 As shown in Figure 7 (upper panel), exposure to oxyHb reduced relaxations but potentiated contractions caused by substance P. The contractions were abolished by endothelium denudation and were reversed to relaxations by indomethacin, a cyclooxygenase inhibitor. Our previous study demonstrated that substance P elicits contractions in dog cerebral arteries, possibly by releasing vasoconstrictor prostaglandins such as PGF^, PGE,, PGD 2 , and PGA 2 from endothelial cells 14 and elicits relaxations via a mediation of EDRF and PGI 2 produced in smooth muscle cells. Relaxations caused by TRK-100 were also reduced by oxyHb.…”

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…Therefore, SR49059 may represent a potential therapeutic agent in the treatment of cerebral vasospasms (373,507). It should be noted that a part of the intracranial artery causes vasodilatation upon AVP stimulation in an endothelium-dependent manner (264,386 Cerebral edema is a devastating consequence of brain injury that leads to compromised cerebral blood flow and worsening parenchymal damage. Blockade of the V1a receptor by SR49059 has been shown to significantly reduce intracranial pressure or cerebral edema after cortical contusion injury, intracerebral hemorrhage injury, or cerebral artery occlusion in animal models (275,322,384,457,487).…”

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

“…Since the relaxation to nerve stimulation is not influenced in feline arteries by endothelium denudation (Saito et al, 1989;Ayajiki et al, 1994), acetylcholine appears not to mediate the response in feline cerebral arteries. Substance P, an EDRF-mediated cerebral vasodilator (Conner and Feniuk, 1987;Onoue et al, 1988), can therefore be excluded as a transmitter candidate.…”

“…Methemoglobin was much less potent in scavenging NO (Martin et al, 1985b). In isolated, perfused rabbit basilar and dog femoral arteries, it was noted that extraluminal application of oxyHb interfered with the relaxation mediated by NO liberated from the endothelium, although the extent was less than that induced by intraluminal application (Hongo et al, 1988;Toda et al, 1988;Tsuji et al, 1989). The difference in vasoconstrictions in response to oxyHb and L-NA in vivo would be due to non-NO compounds such as vasoconstrictor prostanoids (Toda et al, 1980(Toda et al, , 1991aOkamoto et al, 1984;Fujiwara et al, 1984), free radicals, such as superoxide anions (Katusic and Vanhoutte, 1989) and hydroxyl radicals (Steele et al, 1991), endothelin-1 (Cooks et al, 1991Matsumura et al, 1991;Itoh et al, 1994), etc.…”