Apocynin reduces blood pressure and restores the proper function of vascular endothelium in SHR.

This study has evaluated how the vascular endothelium of hypertensive rats chronically treated with apocynin affects acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (PE) action on the nitric oxide (NO) signal transduction pathway in endothelial (EC) and vascular smooth muscle cells. Treatment with apocynin significantly reduced the mean arterial pressure in spontaneously hypertensive rats (SHR). In addition, apocynin improved the impaired ACh hypotensive effect on SHR. Although systemic oxidative stress was high in SHR, SHR treated with apocynin and normotensive rats presented similar systemic oxidative stress levels. Endothelium significantly blunted PE contractions in intact aortas of treated SHR. The ACh effect was impaired in resistance arteries and aortas of SHR, but this same effect was improved in treated SHR. The SNP potency was higher in intact resistance arteries of treated SHR than in intact resistance arteries of untreated SHR. NO and calcium concentrations increased, whereas reactive oxygen species levels decreased in EC of treated SHR. Aortas of untreated and treated SHR did not differ in terms of sGC alpha or beta units expression. Aorta of treated SHR expressed higher eNOS levels as compared to aorta of untreated SHR. The study groups did not differ with respect to NOX1, NOXO1, or NOX4 expression. However, treatment with apocynin normalized overexpression of NOX2 and its subunit p47phox in aortas of SHR. Based on all the results presented in this study, we suggest apocynin increases NO biovailability by different mechanisms, restoring the proper function of vascular endothelium in SHR.

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

The endothelium impairs the vasodilator effect of Ru(terpy)(bdq)NO](3+) (TERPY) in Wistar rat aortas. We hypothesized that endothelial dysfunction could modulate TERPY׳s effect in spontaneously hypertensive rats. The present study investigated the role of the endothelium in the hypotensive and vasodilator effects of TERPY in spontaneously hypertensive rats. We observed a higher hypotensive effect of TERPY in spontaneously hypertensive than in Wistar rats. l-N(G)-Nitroarginine methyl ester, a nitric oxide synthase inhibitor, increased TERPY׳s hypotensive effect in Wistar but not in spontaneously hypertensive rats. TERPY induced a concentration-dependent vasodilator effect in aortas of both rat models. Endothelium removal or l-NAME increased TERPY׳s potency in Wistar rat aortas; this effect was decreased in spontaneously hypertensive rats. TERPY increased nitric oxide level in spontaneously hypertensive rat endothelial cells; this increase was abolished in the presence of l-NAME. In contrast, this effect was increased in Wistar rats. TERPY, with or without l-NAME, decreased levels of reactive oxygen species in spontaneously hypertensive rat endothelial cells. However, it increased these levels in Wistar rats. TERPY reduced aortic endothelial nitric oxide synthase expression in Wistar rats, but did not alter its expression in spontaneously hypertensive rats. In conclusion, different mechanisms underlie the hypotensive and vasodilator effects of TERPY in these two rat models. TERPY reduced endothelial nitric oxide synthase expression and increased reactive oxygen species production in Wistar rat aortas, but did not alter these in spontaneously hypertensive rats. Furthermore, the nitric oxide released by TERPY reacts with reactive oxygen species, decreasing their bioavailability in spontaneously hypertensive rats.

The hypotensive effect of the ruthenium complex [Ru(terpy)(bdq)NO]³âº is higher in male than in female spontaneously hypertensive rats (SHR).

We have previously demonstrated that the hypotensive effect of the ruthenium complex [Ru(terpy)(bdq)NO](3+) (TERPY) is slow, long lasting, and does not lead to reflex tachycardia. TERPY's hypotensive effect is increased in hypertensive rats (SHR or 2 kidney-1clip) compared with normotensive rats. We hypothesized that sexual differences could interfere in the hypotensive effects of nitric oxide (NO) donors in SHR. Therefore, here we aimed to investigate the role of sexual differences and endogenous NO in the hypotension induced by TERPY. In conscious, unrestrained animals, we evaluated the hypotensive effect of TERPY before and after the administration of N-nitro-L-arginine methyl ester (L-NAME) (nonselective NO synthase inhibitor), APOCYNIN (NADPH/NOX inhibitor), and TEMPOL (superoxide dismutase mimetic). The hypotensive effect of TERPY was higher in male than in female SHR, but this difference was not observed in the normotensive Wistar group. The effect of TERPY increased after administration of L-NAME in Wistar rats; however, this effect was not altered by L-NAME in SHR. In SHR, sexual dimorphism in TERPY effect was still observed in animals treated with L-NAME. TEMPOL increases the effect of TERPY only in female SHR. After TEMPOL, the sexual dimorphism in TERPY effect was abolished in the SHR group. APOCYNIN increased the effect of TERPY in male and female Wistar and SHR, but maintained the previously observed difference between male and female SHR. Thus, this study shows that TERPY's hypotensive effect increased in male compared with female SHR and indicates that sexual dimorphism in TERPY effect is associated with oxidative stress.