Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence?

Abstract

Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

History of vascular reactivity models and their involvement in hypertension pathogenesis

“…Hypertension was one of the fi rst diseases associated with decreased bioavailability of nitric oxide (NO) [1], gaining prominence in the development of hypertension models, specifi cally related to inhibition of NO synthesis [23]. The NO synthesis inhibition occurs by analogues of L-arginine, as N G -monomethyl-L-arginine methyl ester (L-NAME) through competition with L-arginine by the NO synthase enzyme (e-NOS) [23].…”

“…Changes in the properties of these factors lead to en-dothelial dysfunction, contributing to the increase in vascular resistance and consequent tone changing, favouring the hypertensive process [1].…”

“…Therefore, scientists began to elucidate the activity and interaction between these substances, aiming to unravel the pathogenesis of hypertensive disease, not only in large vessels such as aorta [1], but also in other beds like splenic movement [35,36] and microcirculation [37]. In this fashion, many complexes with relaxing factors and endothelial contractile action were synthesized and tested in order to formulate new drugs to aid hypertension treatment [38,39], starring the importance of substances released by the endothelium.…”

“…The World Health Organization data record about 17 million deaths per year, highlighting 9.4 million due to hypertension complications [1]. However, access to antihypertensive therapy has increased longevity for the hypertensive population [2].…”

Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International Normalized Ratio (INR) as Predictive Factors of Coagulopathy in Newly Diagnosed Hypertensive Patients

“…Usually hypertension present with complication and unwanted events; for example myocardial infarction and cerebral hemorrhage [1,2]. Cardiovascular diseases are the main cause for the majority of deaths with arterial hypertension being one of the most frequent risk factors [3][4][5]. Coagulopathy and hemostatic dysfunctions are among common complications of hypertension.…”