Endothelin, sex and hypertension

Abstract

The ETs (endothelins) comprise a family of three 21-amino-acid peptides (ET-1, ET-2 and ET-3) and 31-amino-acid ETs (ET-1(1-31), ET-2(1-31) and ET-3(1-31)). ET-1 is synthesized from a biologically inactive precursor, big ET-1, by ECEs (ET-converting enzymes). The actions of ET-1 are mediated through activation of the G-protein-coupled ET(A) and ET(B) receptors, which are found in a variety of cells in the cardiovascular and renal systems. ET-1 has potent vasoconstrictor, mitogenic, pro-inflammatory and antinatriuretic properties, which have been implicated in the pathophysiology of a number of cardiovascular diseases. Overexpression of ET-1 has been consistently described in salt-sensitive models of hypertension and in models of renal failure, and has been associated with disease progression. Sex differences are observed in many aspects of mammalian cardiovascular function and pathology. Hypertension, as well as other cardiovascular diseases, is more common in men than in women of similar age. In experimental models of hypertension, males develop an earlier and more severe form of hypertension than do females. Although the reasons for these differences are not well established, the effects of gonadal hormones on arterial, neural and renal mechanisms that control blood pressure are considered contributing factors. Sex differences in the ET-1 pathway, with males displaying higher ET-1 levels, greater ET-1-mediated vasoconstrictor and enhanced pressor responses in comparison with females, are addressed in the present review. Sex-associated differences in the number and function of ET(B) receptors appear to be particularly important in the specific characteristics of hypertension between females and males. Although the gonadal hormones modulate some of the differences in the ET pathway in the cardiovascular system, a better understanding of the exact mechanisms involved in sex-related differences in this peptidergic system is needed. With further insights into these differences, we may learn that men and women could require different antihypertensive regimens.

Oestradiol ameliorates monocrotaline pulmonary hypertensionviaNO, prostacyclin and endothelin-1 pathways

“…One possible reason is that MCT potentially has a direct influence on the regulation of COX-2 by E 2 ; another possible reason is that the adjustment mechanisms of E 2 may be cellspecific. It is known that oestrogen modulates both ET-1 gene expression and production [29]. Our data indicate that E 2 not only regulates eNOS and COX-2 expressions, but also reduces ECE levels in MCT-treated rats.…”

Endothelin ETB Receptor Is Involved in Sex Differences in the Development of Balloon Injury-Induced Neointimal Formation

“…It has been reported that ET-1 systems are involved in the sex differences in the incidence of cardiovascular disease, especially hypertension (Tostes et al, 2008). We have also demonstrated that female rats were more resistant to deoxycorticosterone acetate salt-induced hypertension than male rats and this sex difference was abolished by genetic deficiency of the ET B receptor (Kawanishi et al, 2007).…”

Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK_Ca Channel Activity

“…[5][6][7] It has been shown that endogenous vasoactive peptides such as angiotensin II, endothelin-1, urotensin II, and natriuretic peptides play an important role in the regulation of vascular tone in (patho) physiological conditions. [8][9][10][11] Several reports suggested that the signalings of vasoactive peptides, including their production, metabolism, and affected vascular functions, are altered in arteries from hypertensive patients and animal models. 6,10,12) Therefore, the manipulation of vasoactive peptide signaling is one of the most important strategies against the development of vascular dysfunction in hypertension.…”