Endothelium-dependent constriction demonstrated in vivo in mouse cerebral arterioles.

Abstract

Endothelium-dependent constriction in mouse pial arterioles was demonstrated by testing contractile responses before and after endothelial injury. All responses were monitored at the same site as the injury. Injury was produced in vivo by exposing an arteriole on the brain surface to the beam of a 6-mW helium-neon laser after first sensitizing the micro vascular bed to the laser energy by injecting Evans blue intravenously. The contractile response to serotonin creatinine sulfate (20 /tg/ml) and to sodium arachidonate (30 /ig/ml) was monitored in vivo with an Image splitter and TV microscope. The responses before laser injury were always constriction; the responses after laser injury were always relaxation. After laser injury, acetykholine chloride (80 /ig/ml) constricted every vessel tested at the injured site. Thus, the injured segment had not lost the capacity to constrict even though neither serotonin nor arachidonate remained able to induce a constriction. The endothelium-dependent constrictions to serotonin or arachidonate were also blocked by pretreatment of the mouse with cyclooxygenase inhibitors, acetylsaUcylic acid (100 mg/kg i.p.) or indomethacin (5 mg/kg). The data suggests that endothelium-dependent constriction to serotonin is mediated by release of arachidonate from the endothelial cell and conversion of that arachidonate by cyclooxygenase to some constricting prostanoid. (Circulation Research 1988;63:837-843) T he study of vascular physiology has been greatly altered by the relatively recent discovery that endothelial cell products mediate dilation by many agonists. '-3 The agonists involved differ somewhat depending on animal species and on the particular vascular bed within a species. '-5 The number and nature of the endothelium-derived relaxing factors that actually control the dilations in question have not yet been resolved.6 -' 2 The existence of endotheliumdependent constriction has also been reported but in relatively few investigations. n~22The evidence for both endothelium-dependent constriction and dilation was originally based on in vitro studies of large vessels. A major method used to establish the existence of these phenomena has been to destroy a portion of the endothelial cells and to demonstrate altered relaxation or constriction to selected agonists while the effects of other

Endothelium-Derived Relaxing Factor Inhibits Constrictor Responses of Large Cerebral Arteries to Serotonin

“…The findings of Rosenblum and Nelson (1988) suggest that serotonin produces en dothelium-dependent constriction in the microcir culation and that endothelial dysfunction may in hibit, not augment, constrictor responses to seroto nin.…”

“…Both constriction and dilation of pial arterioles has been observed (Parsons, 1991). Rosenblum and Nelson (1988) pro vided evidence that suggests that serotonin pro duces modest constriction of pial arterioles that is abolished by injury to the endothelium. Thus, in pial arterioles, endothelium may not inhibit con striction to serotonin by release of EDRF.…”

Hyperlipidemia Promotes Thrombosis After Injury to Atherosclerotic Vessels in Apolipoprotein E–Deficient Mice

“…Photochemical injury is a relatively noninvasive method of inducing endothelial injury and thrombosis that is particularly useful for small animals such as mice. 8,19,20 In addition, the endothelial injury elicited by rose bengal is mediated by a superoxide anion, 21 a type of injury that may occur endogenously in the progression of atherosclerosis 22 and contribute to plaque disruption.…”

“…Photochemical injury is a relatively noninvasive method of inducing endothelial injury and thrombosis that is particularly useful for small animals such as mice. 8,19,20 In addition, the endothelial injury elicited by rose bengal is mediated by a superoxide anion, 21 a type of injury that may occur endogenously in the progression of atherosclerosis 22 and contribute to plaque disruption.Our data indicate that hyperlipidemia induced by high fat feeding in apoE Ϫ/Ϫ mice promotes occlusive thrombus formation after vascular injury. The brief period of high fat feeding in these experiments produced a relatively modest elevation of cholesterol, approximately one third the level attained with more prolonged feeding.…”

Estrogen Restores Postischemic Sensitivity to the Thromboxane Mimetic U46619 in Rat Pial Artery

“…In previous work with the same model, E2 failed to restore postischemic contractile response to 5-HT (Watanabe et al, 2001). However, 5-HT has been shown to induce contraction via endothelial-mediated mechanisms (Rosenblum and Nelson, 1988), while U46619 acts at the level of vascular smooth muscle and requires both extracellular and intracellular calcium (Liu et al, 1997;Moffatt and Cocks, 2004). Therefore, our current data suggest that E2 modulates signaling within vascular smooth muscle, perhaps via a calciummediated mechanism.…”