Nitrergic perivascular innervation in health and diseases: Focus on vascular tone regulation

Abstract

For a long time, the vascular tone was considered to be regulated exclusively by tonic innervation of vasoconstrictor adrenergic nerves. However, accumulating experimental evidence has revealed the existence of nerves mediating vasodilatation, including perivascular nitrergic nerves (PNN), in a wide variety of mammalian species. Functioning of nitrergic vasodilator nerves is evidenced in several territories, including cerebral, mesenteric, pulmonary, renal, penile, uterine and cutaneous arteries. Nitric oxide (NO) is the main neurogenic vasodilator in cerebral arteries and acts as a counter‐regulatory mechanism for adrenergic vasoconstriction in other vascular territories. In the penis, NO relaxes the vascular and cavernous smooth muscles leading to penile erection. Furthermore, when interacting with other perivascular nerves, NO can act as a neuromodulator. PNN dysfunction is involved in the genesis and maintenance of vascular disorders associated with arterial and portal hypertension, diabetes, ageing, obesity, cirrhosis and hormonal changes. For example defective nitrergic function contributes to enhanced sympathetic neurotransmission, vasoconstriction and blood pressure in some animal models of hypertension. In diabetic animals and humans, dysfunctional nitrergic neurotransmission in the corpus cavernosum is associated with erectile dysfunction. However, in some vascular beds of hypertensive and diabetic animals, an increased PNN function has been described as a compensatory mechanism to the increased vascular resistance. The present review summarizes current understanding on the role of PNN in control of vascular tone, its alterations under different conditions and the associated mechanisms. The knowledge of these changes can serve to better understand the mechanisms involved in these disorders and help in planning new treatments.

Priapism following a juvenile Russell’s viper bite: An unusual case report

“…Arachnid envenomation appears to be due to delayed inactivation of sodium channels and downstream calcium flux in corpus cavernosum tissue leading to activation of nitric oxide (NO) synthase (NOS) [9,11,12]. The possible mechanism for penile erection following Russell's viper envenomation may be due to 1 or more toxins of this venom having an effect on molecules such as NO [13], phosphodiesterases (PDE) [14], ion channels, and/or N-methyl-D-aspartate (NMDA) [15] receptors in penile nitrergic nerves present in human corpus cavernosa as they have been shown to play significant roles in the regulation of erection. However, as venoms from juvenile Russell's vipers display reduced expression of proteins [16] and defibrinating enzymes such as ancrod and batroxobin from other vipers have been proposed to treat priapism in humans [17,18], it might be possible that the toxins responsible for this effect may be counteracted in older snakes or only expressed in venoms of juvenile snakes.…”

A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism

“…Perivascular mesenteric innervation plays a relevant role in generating and maintaining mesenteric vascular resistance [ 21 , 22 ]. We have previously reported that the endothelium-derived vasoactive factors angiotensin II or endothelin, whose function can be altered by hyperthyroidism, can modify the perivascular innervation function [ 11 , 12 , 33 , 34 ].…”

“…The mesenteric vasculature plays a relevant role in generating and maintaining vascular resistance [ 44 ]. Among the mechanisms implicated in the maintenance and regulation of vascular resistance, perivascular innervation has an important function in regulating vascular tone [ 21 , 22 ]. There is a rich functional innervation in SMA.…”

“…Inadequate mesenteric blood flow and tissue perfusion can induce relevant hemodynamic changes [ 19 , 20 ]. The superior mesenteric artery (SMA) has rich and functional sympathetic and nitrergic nerve endings [ 21 , 22 ], which release noradrenaline (NA) and ATP, and NO, respectively. The implication of each of these innervations depends on the synthesis, release, response and metabolism of the different neurotransmitters, which have been reported to change in different pathophysiological situations.…”

Exercise‐mediated autophagy in cardiovascular diseases

“…The endothelium controls many vascular adaptive processes, and impaired endothelial function associated with impaired nitric oxide (NO) synthesis and/or bioavailability is considered the first step in the progression of CVDs. 3,4 Here, the impact of age and sex on CVDs is becoming increasingly clear, yet important intracellular processes remain poorly understood. 5 Autophagy is a degradation system regulated by autophagy-related genes where intracellular proteins and organelles that are damaged, denatured, or aged are transported into lysosomes for digestion and degradation.…”