Effect of aging on endothelium-dependent vascular relaxation of isolated human basilar artery to thrombin and bradykinin.

Abstract

Using strips of human basilar arteries mounted in organ chambers to record isometric tension, we investigated vascular reactivity to thrombin and bradykinin. Both agents produced endothelium-dependent relaxation of basilar artery strips precontracted with phenylephrine but had no effect on resting tension in strips with or without endotheUum. The relaxations caused by thrombin were abolished by antithrombin III/heparin, hirudin, and MD805. Thrombin but not bradykinin caused complete tachyphylaxis toward a second exposure. Indomethacin did not inhibit the relaxations induced by thrombin or bradykinin, whereas bromophenacyl bromide and methylene blue did. Aging decreased the relaxation induced by thrombin but did not affect the concentration needed to reach 50% maximal relaxation, nor did it affect the maximal relaxation in response to bradykinin, calcium ionophore A23187, and sodium nitroprusside. Our results suggest that thrombin and bradykinin produce endothelium-dependent relaxations mediated by an endothelium-derived relaxing substance and that the relaxation caused by thrombin is mediated by a proteolytic action on endothelial cells. The decrease in relaxations in response to thrombin with increasing age might be due to a decrease in the number or sensitivity of thrombin receptors on endothelial cells. (Stroke 1990;21:1039-1043) A endothelium-derived relaxing substance, discovered by Furchgott and Zawadski 12 and usually called endothelium-derived relaxing factor (EDRF), mediates endothelium-dependent relaxation in response to a number of vasoactive substances. The relaxation decreases in pathophysiological states, such as hypertension 3 and atherosclerosis, 4 and with increasing age, as found in isolated preparations from dogs 5 and rats. 6 We do not know whether the results in experimental animals are applicable to isolated human arteries since there are few studies on this subject.In isolated human basilar arteries, thrombin and bradykinin have recently been shown to induce endothelium-dependent relaxation. 7 -8 Because both vasodilators are known to be generated during blood coagulation, it is important to consider whether vascular responsiveness to them changes with age. The aim of our study was therefore to

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

“…This is in accordance with previous results reported by us and others Csiszar et al 2007a;Blackwell et al 2004;Modrick et al 2009;Hatake et al 1990). Lifelong CR completely prevented this age-related decline in EDD in conduit arteries (carotid), but only partially prevents the decline in cerebral resistance arteries (MCA).…”

“…Older humans and rodents exhibit impaired EDD in conduit arteries as well as cerebral arteries Csiszar et al 2007a;Blackwell et al 2004;Modrick et al 2009;Hatake et al 1990;Eskurza et al 2004;Celermajer et al 1994). It has been shown previously that lifelong CR can prevent the age-related decline in EDD in the aorta (Csiszar et al 2009), but the effect of CR on resistance artery EDD has not been studied.…”

Age‐related changes in endothelial nitric oxide synthase phosphorylation and nitric oxide dependent vasodilation: evidence for a novel mechanism involving sphingomyelinase and ceramide‐activated phosphatase 2A

“…As the altered vasoreactivity observed in rodent models of aging approximate that of humans (Hongo et al, 1988;Hatake et al, 1990;Tschudi et al, 1996), the results currently presented potentially affect a large and growing segment of the population in Western societies -the elderly. The clinical relevance of the present work is heightened by our data showing that pharmacologic inhibition of nSMase with GW4869 significantly improves endothelium-dependent vasodilation in the aged aorta.…”

“…While the mechanisms underlying this risk are largely unknown, deficits in vascular endothelial cell function appear to be a critical factor, leading to impaired vasomotor activity, hypertension and progression of nearly all types of CVD (Lakatta & Levy, 2003;Lakatta, 2003). This agedependent impairment of endothelium-dependent vasorelaxation is not unique to humans having also been observed in numerous animal models (Hongo et al ., 1988;Hatake et al ., 1990;Tschudi et al ., 1996).…”

Substance P‐induced relaxation and hyperpolarization in human cerebral arteries

“…The L-arginine-NO pathway has been demonstrated in cerebral arteries from different animal species (for review, see Faraci, 1992). Although endothelium-dependent relaxation has been observed in human basilar (Whalley et al, 1987;Kanamaru et al, 1989;Hatake et al, 1990), middle cerebral (Martin de Aguilera et al, 1990;Toda, 1990;Conde et al, 1991;Akopov et al, 1992) and pial (Hardebo et al, 1987;Szabo et al, 1992) arteries, the existence of an L-arginine-NO pathway in human isolated cerebral arteries has not been established previously. Endo~thdium and cerebrovascular tone An L-NOARG-resistant relaxation was observed in eight out of 14 patients.…”