The endocrine system in chronic nitric oxide deficiency

Abstract

The experimental model of chronic inhibition of nitric oxide (NO) production has proven to be a useful tool to study cardiovascular and renal lesions produced by this type of hypertension, which are similar to those found in human hypertension. It also offers a unique opportunity to study the interaction of NO with the humoral systems, known to have a role in the normal physiology of vascular tone and renal function. This review provides a thorough and updated analysis of the interactions of NO with the endocrine system. There is special focus on the main vasoactive factors, including the reninangiotensin-aldosterone system, catecholamines, vasopressin, and endothelin among others. Recent discoveries of crosstalk between the endocrine system and NO are also reported. Study of these humoral interactions indicates that NO is a molecule with ubiquitous function and that its inhibition alters virtually to all other known regulatory systems. Thus, hypothyroidism attenuates the pressor effect of NO inhibitor N-nitro-L-arginine methyl ester, whereas hyperthyroidism aggravates the effects of NO synthesis inhibition; the sex hormone environment determines the blood pressure response to NO blockade; NO may play a homeostatic role against the prohypertensive effects of mineralocorticoids, thyroid hormones and insulin; and finally, NO deficiency affects not only blood pressure but also glucose and lipid homeostasis, mimicking the human metabolic syndrome X, suggesting that NO deficiency may be a link between metabolic and cardiovascular disease.

Hormonal modulation of endothelial NO production

“…As this inhibition was identified in placental and chorionic cells, these effects have implications in fetal programming of hypertension especially in male offspring of mothers who are stressed [80]. Other feedback systems of NO on the hypothalamic-pituitary-adrenal axis also have implications for development of cardiovascular disease related to major depressive disorder and stress-induced hypertension [66, 76, 96] and may contribute to sex differences in presentation and etiology of cardiovascular diseases [12, 38]. …”

“…2). A decrease in renin would in turn reduce activation of the angiotensin conversion pathways with potential reductions in angiotensin II (AII) related decreases in endothelial NO bioavailability [79, 87, 96]. Prolactin secretion from the pituitary is enhanced in the presence of estrogen [28, 42, 64].…”

“…Whether or not NO affects release of thyroxin from thyroid follicular cells requires further investigation [96]. Even though T3 (L3,5,3′-triiodothryronine) initiates rapid release of NO from cultured endothelial cells, it is unclear if vascular regulation of NO in the setting of hyper- or hypothyroid conditions reflects the direct influence of the hormone on eNOS or indirect effects of altered glucose and lipid metabolism [17, 31, 96].…”

Effect of Transdermal Nitroglycerin on Insulin Resistance in Healthy Young Men

“…Actually NO providing a link between cardiovascular and metabolic homeostasis [7]. In this regards there are also another reports indicated that elevation of nitric oxide activity is a mechanism for lower incidence of arterial hypertension in females [4,8]. Shangjian, et al also in a study reporting higher levels of serum nitric oxide level as a compensatory mechanism in insulin resistant rats comparing with control group [9].…”

“…Nitric oxide have regulatory effects on insulin and carbohydrate metabolism [2,3]. No playing a regulatory role in hypothalamushypophysis axis and inhibition of prolactin release and regulating secretion of steroids and catecholamines [4].…”