The long-term objective of the investigation is to determine the role of altered endothelial function in the regulation of diameter of skeletal muscle arterioles which may contribute to the elevated peripheral resistance in hypertension and to elucidate the mechanisms causing the alterations. The hypothesis is that altered endothelial mechanotransduction of pressure and sheer stress (enhanced myogenic tone and reduced flow dependent dilation) are among the possible mechanisms responsible for elevated vascular resistance in hypertension. There are three specific aims 1) Determine whether and to what extent the increases in hemodynamic forces, pressure and/or sheer stress, are the cause of the dysfunction of mechanotransduction leading to nitric oxide prostaglandin release from arteriolar, endothelium and hypertension. Forelimb and hind-limb arterioles from coarctation-induced hypertensive rats will be used to differentiate between the effects of elevated hemodynamic forces on the function of arterioles and other confounding factors present in hypertension; 2) To determine the effects of high pressure or sheer stress per se on arterioles utilizing isolated arterioles of normotensive rats. Exposing them to acute high transmural pressure or sheer stress will enable the investigators to distinguish between the endothelial dysfunction induced by pressure and sheer stress; and 3) To determine whether the mechanism by which the elevated hemodynamic forces elicit the endothelial dysfunction is the production of reactive oxygen metabolites. Pharmacological tools interfering with the metabolism of ROMs will be utilized to prevent the high pressure and/or sheer stress induced endothelial dysfunction. In addition, the level of endothelial factors released into the vessel perfusates will be determined in various conditions. The result of this project will yield information regarding the role of endothelial dependent alterations on myogenic and flow dependent regulation of arteriolar tone, which potentially contribute to the development of increased peripheral resistance in hypertension.
| Szekeres, Mária; Nádasy, György L; Dörnyei, Gabriella et al. (2018) Remodeling of Wall Mechanics and the Myogenic Mechanism of Rat Intramural Coronary Arterioles in Response to a Short-Term Daily Exercise Program: Role of Endothelial Factors. J Vasc Res 55:87-97 |
| Koller, Akos; Toth, Peter (2012) Contribution of flow-dependent vasomotor mechanisms to the autoregulation of cerebral blood flow. J Vasc Res 49:375-89 |
| Rutkai, Ibolya; Feher, Attila; Erdei, Nora et al. (2009) Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. Cardiovasc Res 83:148-54 |
