Endothelium and control of vascular function. State of the Art lecture.

Abstract

The response of isolated blood vessels to a variety of vasoactive agonists is modulated by the presence of endothelial cells. Indeed, these cells can release both dilator and constrictor substances. The major endothelium-derived relaxing factor may be nitric oxide, which activates soluble guanylate cyclase in the smooth muscle, although the endothelial cells also secrete an unidentified hyperpolarizing factor. Among the natural stimuli for the release of endotheliumderived relaxing factors are circulating hormones, platelet products, thrombin, shear stress, and certain autacoids. Endothelium-derived relaxing factors may contribute to the regulation of the release of atrial natriuretic factor and renin. The endothelial cells can also release constricting factors; among the likely candidates are superoxide anions or the peptide endothelin. In hypertensive blood vessels, the ability to release endothelium-derived relaxing factors but not endothelium-derived contracting factors is blunted. (Hypertension 1989;13:658-667) A fter the initial report by Furchgott and Zawadzki 1 of the obligatory role of endothelial cells in relaxations of isolated arteries of the rabbit to acetylcholine, vascular physiologists and pharmacologists have been forced to admit that the most intimal layer of the blood vessel wall, in addition to its role in metabolism, coagulation, and transport processes, possesses the ability to profoundly modulate the degree of contraction of the smooth muscle that surrounds it. It does so primarily by the release of short-lived vasodilator and vasoconstrictor substances, termed endotheliumderived relaxing factor (EDRF) and endotheliumderived contracting factor (EDCF), respectively. The ability of the endothelium to control the underlying vascular smooth muscle appears to be an ancestral property of these cells, emerging early in evolution (see Reference 2). This brief review summarizes the author's current thinking on the questions concerning endothelium-dependent modulation-the answers to which could be of particular relevance in hypertension and its treatment.

Inhibition of Acetylcholinesterase Modulates the Autoregulation of Cerebral Blood Flow and Attenuates Ischemic Brain Metabolism in Hypertensive Rats

“…Acetylcholine (ACh) causes significant relaxation of the arteries (Fujii et aI., 1992;Furchgott and Zawadzki, 1980;Vanhoutte, 1989), although the role of ACh in brain during decreases in blood pressure is still under dis cussion. Recently, cholinergic deficits in the brain are considered to have a close relationship with im pairments of cognitive function (Moran et aI., 1994; Perry et aI., 1977; Wilcock et aI., 1982), and the Abbreviations used: ACh, acetylcholine; AChEI, acetylcho linesterase inhibitor; ANOY A, analysis of variance; EDRF, en dothelium-derived relaxing factor; MAP, mean arterial pressure; SHR, spontaneously hypertensive rats.…”

Endothelial dysfunction and hypertension in aging

“…21 In addition, it is well known that the endothelium secretes various vasoactive agents, such as the vasodilators NO, prostacyclin and endothelium-derived hyperpolarizing factor and the vasoconstrictors, such as endothelin-1, angiotensin II (Ang II) and thromboxane A 2 . [22][23][24][25] It is concluded that the endothelium is the biggest endocrine organ in the human body. A healthy endothelium maintains vascular tone and structure by regulating the balance between vasodilation and vasoconstriction, growth inhibition and growth promotion, antithrombosis and prothrombosis, anti-inflammation and proinflammation, and also antioxidation and pro-oxidation.…”

“…A healthy endothelium maintains vascular tone and structure by regulating the balance between vasodilation and vasoconstriction, growth inhibition and growth promotion, antithrombosis and prothrombosis, anti-inflammation and proinflammation, and also antioxidation and pro-oxidation. [23][24][25][26] The simple molecule NO regulates basal vascular tone, at least in part, by about 50% in the brachial artery in humans. 11,26 Thus, loss of healthy endothelial function becomes a trigger of atherosclerosis.…”

Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure

“…Impaired flow-mediated dilatation (FMD) in the brachial artery is characterised by loss of endothelium-dependent vascular smooth muscle relaxation in response to vasodilator stimuli (1). The resultant effect of this impairment may be partly due to alterations in the nitric oxide (NO) pathway, notably a reduction in endotheliumderived NO bioavailability (2)(3).…”