Contrasting Effects of Angiotensin Type 1 and 2 Receptors on Nitric Oxide Release under Pressure.

Abstract

This study was designed to test the hypothesis that increased pressure itself could cause endothelial dysfunction and lead to decreased nitric oxide (NO) release, partly through effects on the tissue renin angiotensin system in hypertension. Cultured endothelial cells (ECs) isolated from the aortas of WKY rats were continuously exposed to a pressure of 150 mmHg in a CO2 incubator for 72 h using a pressure system, and the NOx (NO2 and NO3) and angiotensin II (Ang II) concentrations in the supernatant were measured. An Ang decreased in patients with secondary hypertension (3), and antihypertensive therapy can improve EDR (4, 5); moreover, we have demonstrated that lowering pressure improves NO release from the ECs of hypertensive rats (6). Thus high blood pressure itself may promote endothelial dysfunction.There are two very important modulators of endothelial NO release; one consists of direct hemodynamic changes and the other of humoral factors such as the renin-angiotensin system (RAS). Endothelial cells (ECs) lining the vessel lumen are exposed to various mechanical forces, including shear stress, stretch, and transmural pressure, which are produced by blood pressure and blood flow. These hemodynamic forces are known to elicit many important physio-

Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow

“…Indeed, it has been shown that mitotic ECs along the aorta are found almost exclusively at the base of arterial branches, indicating that endothelial proliferation is particularly high around bifurcations (32). It is noteworthy that hypertension, a well-recognized risk factor of aneurysm development, is believed to reduce the bioavailability of NO (12,23), and we find that NO is necessary for the WSS-stimulated proliferation. Reduced NO bioavailability could disrupt the protective responses in ECs elicited by high WSS, rendering regions such as apices of bifurcations and sharp curvatures more susceptible to mechanical damage when subjected to sustained hemodynamic stress.…”

Effects of Bradykinin on Cardiovascular Remodeling in Renovascular Hypertensive Rats

“…Several studies have shown that the production of NO or up-regulation of endothelial NOS (eNOS) activity plays a role in preventing cardiac abnormalities, such as ischemic injury and cardiac hypertrophy (5,27). In the present study, the inhibition of NOS by treatment with L-NAME completely blocked the cardioprotection of BK.…”

Early upregulation of iNOS mRNA expression and increase in NO metabolites in pressurized renal epithelial cells

“…A similar increase was noted in the rat (NRK-52 E) cells when subjected to pressures of (60 and 120 mmHg) for 60 and 120 min. In contrast, rat endothelial cells pressurized for 72 h at 150 mmHg had decreased NO levels, increased ANG II, and expression of ANG II receptor 2 (ATR2) (14). ANG II acting via ATR2 is believed to suppress NO in these pressurized endothelial cells.…”

“…Mechanotransduction of the signal mediates the effects of pressure on NOS (7,14,26,32). Increased amounts of NO are released by articular cartilage, periodontal ligament fibroblasts, and trabecular cells, when stimulated by static and intermittent pressure (7,26,32).…”