Different vasoactive effects of chronic endothelial and neuronal NO-synthase inhibition in young Wistar rats

Abstract

While the unequivocal pattern of endothelial nitric oxide synthase (eNOS) inhibition in cardiovascular control is recognized, the role of NO produced by neuronal NOS (nNOS) remains unclear. The aim of this study was to compare the effects of chronic treatment with 7-nitroindazole (7-NI, nNOS inhibitor) and N(G)-nitro-L-arginine methylester (L-NAME, general and predominantly eNOS inhibitor) on cardiovascular system of young normotensive rats. Wistar rats (4 weeks old) were used: controls and rats administered either 7-NI (10 mg/kg bw/day) or L-NAME (50 mg/kg bw/day) in drinking water for 6 weeks. The systolic blood pressure (sBP) was measured by plethysmographic method, and the vasoactivity of isolated arteries was recorded. 7-NI-treatment did not affect sBP; however, the sBP was increased after L-NAME-treatment. L-NAME inhibited acetylcholine-induced relaxation of thoracic aorta (TA), whereas it remained unchanged after 7-NI-treatment. The response of TA to sodium nitroprusside was increased in both experimental groups. The expression of eNOS and nNOS in TA was unchanged in both experimental groups, whereas the activity of NOS was decreased in L-NAME-treated group. Noradrenaline- and angiotensin II-induced contractions of TA were reduced in L-NAME-treated group; however, the contractions remained unchanged in 7-NI-treated group. In all groups, the endogenous angiotensin II participated in adrenergic contraction of TA; this contribution was significantly increased in L-NAME-treated group. Neurogenic contractions in mesenteric artery (MA) remained unchanged after 7-NI-treatment, but increased after L-NAME-treatment. Results show that NO deficiency induced by administration of 7-NI and L-NAME had different cardiovascular effects: eNOS and nNOS triggered distinct signaling pathways in young normotensive rats.

Early Supplementation of d‐Cysteine or l‐Cysteine Prevents Hypertension and Kidney Damage in Spontaneously Hypertensive Rats Exposed to High‐Salt Intake

“…A numbers of observations support BP‐lowering effects of exogeneous H 2 S in a variety of animal models of hypertension . Less attention has been paid to the antihypertensive effect of endogenous H 2 S, especially from d‐ cysteine .…”

Blood Pressure Regulation in Stress: Focus on Nitric Oxide-Dependent Mechanisms

“…In contrast to chronic L-NAME treatment, chronic administration of structurally different NOS inhibitor, 7-nitroindazole (7-NI), failed to affect BP in normotensive Wistar and spontaneously hypertensive rats (SHR) (Cacanyiova et al 2012, Cacanyiova et al 2014, Kristek et al 2015. Moreover, chronic L-NAME administration inhibited endothelium-dependent relaxation of the thoracic aorta, whereas it remained unchanged after chronic 7-NI treatment in Wistar and SHR rats (Cacanyiova et al 2012, Cacanyiova et al 2014).…”

“…In contrast to chronic L-NAME treatment, chronic administration of structurally different NOS inhibitor, 7-nitroindazole (7-NI), failed to affect BP in normotensive Wistar and spontaneously hypertensive rats (SHR) (Cacanyiova et al 2012, Cacanyiova et al 2014, Kristek et al 2015. Moreover, chronic L-NAME administration inhibited endothelium-dependent relaxation of the thoracic aorta, whereas it remained unchanged after chronic 7-NI treatment in Wistar and SHR rats (Cacanyiova et al 2012, Cacanyiova et al 2014). In addition, neurogenic contractions (induced by transmural nerve stimulation of nerve endings and mediated by endogenous noradrenaline) in mesenteric artery remained unchanged after 7-NI-treatment, but increased after L-NAME-treatment (Cacanyiova et al 2012, Cacanyiova et al 2014).…”

“…Moreover, chronic L-NAME administration inhibited endothelium-dependent relaxation of the thoracic aorta, whereas it remained unchanged after chronic 7-NI treatment in Wistar and SHR rats (Cacanyiova et al 2012, Cacanyiova et al 2014). In addition, neurogenic contractions (induced by transmural nerve stimulation of nerve endings and mediated by endogenous noradrenaline) in mesenteric artery remained unchanged after 7-NI-treatment, but increased after L-NAME-treatment (Cacanyiova et al 2012, Cacanyiova et al 2014). As 7-NI is believed to inhibit predominantly nNOS (Gulati et al 2006, Cacanyiova et al 2014, the roles of eNOS-derived NO and nNOS-derived NO in BP regulation seem to be different.…”

“…In addition, neurogenic contractions (induced by transmural nerve stimulation of nerve endings and mediated by endogenous noradrenaline) in mesenteric artery remained unchanged after 7-NI-treatment, but increased after L-NAME-treatment (Cacanyiova et al 2012, Cacanyiova et al 2014). As 7-NI is believed to inhibit predominantly nNOS (Gulati et al 2006, Cacanyiova et al 2014, the roles of eNOS-derived NO and nNOS-derived NO in BP regulation seem to be different. However, it has to be noted that despite enormous effort of researchers to find the substances which would be absolutely specific for either nNOS or eNOS, which would allow us to distinguish NO produced by nNOS from NO produced by eNOS under chronic in vivo conditions, are still not available (Alderton et al 2001, Víteček et al 2012.…”