Endothelium negatively modulates the vascular relaxation induced by nitric oxide donor, due to uncoupling NO synthase

Photocytotoxic activity of a nitrosyl phthalocyanine ruthenium complex — A system capable of producing nitric oxide and singlet oxygen

“…To test this hypothesis, [Ru(NO)(ONO)(pc)] was employed as a vasodilator agent because nitrosyl ruthenium compounds have been extensively reported as NO donors that induce rat aorta relaxation [18,61,62]. Fig.…”

Mechanisms underlying the hypotensive and vasodilator effects of Ru(terpy)(bdq)NO]3+, a nitric oxide donor, differ between normotensive and spontaneously hypertensive rats

“…Recent findings have shown that endothelial nitric oxide synthase activity can modulate vasodilation induced by nitric oxide donors such as SNP or TERPY (Bonaventura et al, 2008(Bonaventura et al, , 2009. The results of Bonaventura et al (2008) provide strong evidence that SNP induces the production of nitric oxide by endothelial cells in normotensive rat aortas through nitric oxide synthase activation.…”

“…Moreover, whereas in aortas from normotensive Wistar rats TERPY reduced endothelial nitric oxide synthase expression, this is not seen in aortas of spontaneously hypertensive rats. Some evidences suggested that the endothelium could modulate nitric oxide donor effects (Bonaventura et al, 2008(Bonaventura et al, , 2009). This can be explained by the fact that endothelium-derived factors and nitric oxide donors share common pathways in vascular smooth muscle relaxation (Miller and Megson, 2007).…”

“…As a particular mechanism of action of TERPY, it was demonstrated that TERPY could degrade tetrahydrobiopterin to dihydrobiopterin in aortas of normotensive Wistar rats (Bonaventura et al, 2009). Decreased levels of tetrahydrobiopterin, an essential cofactor for nitric oxide synthase activity, lead to the uncoupling of the nitric oxide synthase dimer (Cosentino and Luscher, 1999;Katusic, 2001;Stroes et al, 1998;Vasquez-Vivar et al, 1998).…”

“…The results of Bonaventura et al (2008) provide strong evidence that SNP induces the production of nitric oxide by endothelial cells in normotensive rat aortas through nitric oxide synthase activation. On the other hand, the relaxation induced by TERPY is impaired in aortic rings with intact endothelium of normotensive Wistar rats due to nitric oxide synthase uncoupling induced by TERPY (Bonaventura et al, 2009). When uncoupled, nitric oxide synthase leads to the production of superoxide anion and/or hydrogen peroxide (Kietadisorn et al, 2012;Montezano and Touyz, 2012).…”