Vascular Dilation Responses of Rat Small Mesenteric Arteries at High Intravascular Pressure in Spontaneously Hypertensive Rats

Abstract

ypertension is a multifactorial, polygenic disease and is an important risk factor for the development of atherosclerosis and cardiovascular diseases. [1][2][3][4] It is well established that chronic hypertension is associated with the structural and functional changes in the resistance vasculature that are responsible for the elevated peripheral resistance in hypertension; 1,5,6 such structural alterations are termed "vascular remodeling". In the majority of hypertension models studied, the internal diameter is reduced and the wall/lumen ratio is increased in small arteries as a consequence of increased wall thickness. Vascular remodeling is also associated with altered mechanical properties such as reduced distensibility. [5][6][7] In addition, the altered balance of vasoconstrictor and vasodilator systems has an important role in augmenting systemic resistance in hypertension. 8,9 In vitro studies of small arteries from hypertensive animals and humans are widely used in the investigation of hypertension and its complications. Two experimental techniques are commonly used: (1) wire myography and (2) pressurized myography systems. 10,11 The pressurized method has several advantages, including maintenance of the vessel's cylindrical shape and better preservation of the endothelium. The structural and mechanical characteristics of the small arteries of both normotensive and hypertensive rats and humans have been evaluated at different levels of intravascular pressure by the pressurized myography technique. [11][12][13][14][15] In those studies, the small arteries obtained from hypertensive subjects were exposed to intraluminal pressures within a wide range (ie, 3-140 mmHg), and structural and mechanical properties, such as internal and external diameters, cross-sectional area, wall/lumen ratio, distensibility, circumferential wall strain or stress, were evaluated. The results have indicated that small arteries from hypertensive subjects have altered structural and mechanical properties compared with normotensives.Pressurized small artery preparations also have been used to examine the functional properties of vessels from normotensive and hypertensive rats or humans. [16][17][18][19][20][21] However, those studies, which investigated the dilatation responses of small arteries to several agonists or flow by pressurized myography, were only performed under normotensive conditions, and the "normotensive" intraluminal pressures differed among them. Small mesenteric arteries (SMA) are usually exposed to pressures of 30 or 45 mmHg, [16][17][18] whereas small arteries obtained from skeletal muscle are exposed to greater pressures. 19 Pressurized small artery preparations also have been used in several human studies: Numerous studies have investigated the mechanical and morphometric properties of small arteries obtained from hypertensive animals and humans. However, the functional properties of resistance arteries from normotensive and hypertensive subjects have only been examined under normotensive conditions. The objec...

Acute Exertion Elicits a H 2 O 2 -Dependent Vasodilator Mechanism in the Microvasculature of Exercise-Trained but Not Sedentary Adults

“…The effects of increased intraluminal pressure and transient hypertension on microvascular function have been studied in both animal models 9-11 and in isolated human arterioles, 7 but this is the first study, to our knowledge, to demonstrate a differential response to a pressure stimulus in the microvasculature of exercise trained and sedentary adults. Because weight lifting causes transient increases in blood pressure, it could be hypothesized that this repeated exposure to elevated blood pressures has a conditioning effect on the vasculature.…”

“…Gündüz and colleagues demonstrated normal ACh- and flow-mediated dilation in mesenteric arteries of spontaneously hypertensive rats after the arteries were exposed to high intraluminal pressure; whereas arteries from normotensive Wistar Kyoto rats showed blunted dilation to both stimulus after exposure to the same high pressure insult. 11 …”

Vascular Smooth Muscle Remodeling in Conductive and Resistance Arteries in Hypertension

“…In humans, counter-regulatory vasodilatory events have also been tested using endothelium-independent agents, such as sodium nitroprusside (SNP), and were not different between control and hypertensive subjects 149,151 . Conversely, endothelial-dependent vasodilation by acetylcholine was impaired in hypertensive patients and animal models, but the amount of experimental variability in these observations may be a red-herring in interpreting the outcome of studies of VSMC function in hypertension 149,152,153 . Nonetheless, it remains critically important to test the complex signaling pathways used to balance vasoconstriction and counteracting vasodilatory forces, which, under pathological conditions cause hyperconstriction, increased vascular resistance, and high blood pressure.…”

Effects of Acute Transmural Pressure Elevation on Endothelium-Dependent Vasodilation in Isolated Rat Mesenteric Veins

“…Previous in vitro studies conducted in pressurized small arteries including MSAs have shown that endothelium-dependent vasodilation [2,3,4,5,9,10] evoked by flow- and receptor-selective agonists is significantly reduced with increases of TMP. Endothelium-independent vasodilation induced by the NO donors, SNP or SNAP, were also reduced by TMP elevation [2,3,4,9]. However, in the present study, the lack of acute pressure effects on BK as well as NO donor-evoked vasodilation suggests that in PGF2α-preconstricted MSVs the activity of endothelial NOS and VSM guanylyl cyclase is not altered.…”

“…Endothelium-dependent vasodilation has been widely investigated in the arteries with some studies showing the presence of endothelium dysfunction in mesenteric small arteries (MSAs) of healthy rats studied in vitro at a high level of transmural pressure (TMP) [2,3]. An impaired endothelial dilator function has also been reported in some disease conditions in arteries [4,5,6,7,8], including studies in rat mesentery [9,10]. The findings of these studies suggest that high levels of TMP may be harmful to the vascular regulatory function of the endothelium mainly via reducing NO function, which has been considered as a major pathogenesis of hypertension.…”