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The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway.

Mendes-Júnior Ld, Guimarães DD, Gadelha DD, Diniz TF, Brandão MC, Athayde-Filho PF, Lemos VS, França-Silva Mdo S, Braga VA - Front Physiol (2015)

Bottom Line: In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 ± 0.1 vs. 5.1 ± 0.1) or by inhibiting KATP channels (pD2 = 4.3 ± 0.1 vs. 5.1 ± 0.1).Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 ± 6 vs. 170 ± 4 mmHg, respectively).Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Center, Federal University of Paraíba João Pessoa, Brazil.

ABSTRACT
We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic treatment with HEX on cardiovascular parameters were evaluated. HEX induced endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 ± 4.1%; potency [pD2] = 5.1 ± 0.1). Relaxation was attenuated by scavenging nitric oxide (ME = 44.9 ± 9.4% vs. 100.4 ± 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 ± 9.7% vs. 100.4 ± 4.1%). In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 ± 0.1 vs. 5.1 ± 0.1) or by inhibiting KATP channels (pD2 = 4.3 ± 0.1 vs. 5.1 ± 0.1). HEX increased NO levels in mesenteric arteries (33.2 ± 2.3 vs. 10.7 ± 0.2 au, p < 0.0001). Intravenous acute administration of HEX (1-20 mg/kg) induced hypotension and bradycardia in normotensive and hypertensive rats. Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 ± 6 vs. 170 ± 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive K(+) channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats.

No MeSH data available.


Related in: MedlinePlus

(A) Representative images of fluorescence in cranial mesenteric artery sections incubated with DAF-2 DA (10 μmol/L), a fluorescent cell permeable probe for NO. (B) Bars graph showing the NO production after incubation with only DAF-2 DA (Baseline) and treatments groups: HEX; nitroglycerin (GTN); HEX + L-NNA; GTN + L-NNA. Fluorescence was quantified by optic densitometry (arbitrary units, a.u.). Results are mean ± s.e.m., n = 5 each group. *p < 0.05 vs. Baseline.
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Figure 2: (A) Representative images of fluorescence in cranial mesenteric artery sections incubated with DAF-2 DA (10 μmol/L), a fluorescent cell permeable probe for NO. (B) Bars graph showing the NO production after incubation with only DAF-2 DA (Baseline) and treatments groups: HEX; nitroglycerin (GTN); HEX + L-NNA; GTN + L-NNA. Fluorescence was quantified by optic densitometry (arbitrary units, a.u.). Results are mean ± s.e.m., n = 5 each group. *p < 0.05 vs. Baseline.

Mentions: Original images from epifluorescence microscopy (Figure 2A) show cranial mesenteric artery sections incubated with DAF-2 DA and the treatments performed. The data plotted on graph (Figure 2B) show at first the baseline fluorescence emitted by the probe without any further treatment (control). After incubation with HEX the fluorescence significantly increased in samples when compared to control (33.23 ± 2.29 vs. 10.66 ± 0.62 a.u., respectively, p < 0.05). The nitroglycerin (GTN), the positive control, also increased the fluorescence (36.92 ± 2.25 vs. 10.66 ± 0.62 a.u., respectively, p < 0.05). Furthermore, L-NNA did not prevent the increase in fluorescence promoted by both HEX (32.77 ± 1.65 vs. 33.23 ± 2.29 a.u., respectively, p > 0.05) and GTN (33.95 ± 1.96 vs. 36.92 ± 2.25 a.u., respectively, p > 0.05).


The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway.

Mendes-Júnior Ld, Guimarães DD, Gadelha DD, Diniz TF, Brandão MC, Athayde-Filho PF, Lemos VS, França-Silva Mdo S, Braga VA - Front Physiol (2015)

(A) Representative images of fluorescence in cranial mesenteric artery sections incubated with DAF-2 DA (10 μmol/L), a fluorescent cell permeable probe for NO. (B) Bars graph showing the NO production after incubation with only DAF-2 DA (Baseline) and treatments groups: HEX; nitroglycerin (GTN); HEX + L-NNA; GTN + L-NNA. Fluorescence was quantified by optic densitometry (arbitrary units, a.u.). Results are mean ± s.e.m., n = 5 each group. *p < 0.05 vs. Baseline.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553900&req=5

Figure 2: (A) Representative images of fluorescence in cranial mesenteric artery sections incubated with DAF-2 DA (10 μmol/L), a fluorescent cell permeable probe for NO. (B) Bars graph showing the NO production after incubation with only DAF-2 DA (Baseline) and treatments groups: HEX; nitroglycerin (GTN); HEX + L-NNA; GTN + L-NNA. Fluorescence was quantified by optic densitometry (arbitrary units, a.u.). Results are mean ± s.e.m., n = 5 each group. *p < 0.05 vs. Baseline.
Mentions: Original images from epifluorescence microscopy (Figure 2A) show cranial mesenteric artery sections incubated with DAF-2 DA and the treatments performed. The data plotted on graph (Figure 2B) show at first the baseline fluorescence emitted by the probe without any further treatment (control). After incubation with HEX the fluorescence significantly increased in samples when compared to control (33.23 ± 2.29 vs. 10.66 ± 0.62 a.u., respectively, p < 0.05). The nitroglycerin (GTN), the positive control, also increased the fluorescence (36.92 ± 2.25 vs. 10.66 ± 0.62 a.u., respectively, p < 0.05). Furthermore, L-NNA did not prevent the increase in fluorescence promoted by both HEX (32.77 ± 1.65 vs. 33.23 ± 2.29 a.u., respectively, p > 0.05) and GTN (33.95 ± 1.96 vs. 36.92 ± 2.25 a.u., respectively, p > 0.05).

Bottom Line: In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 ± 0.1 vs. 5.1 ± 0.1) or by inhibiting KATP channels (pD2 = 4.3 ± 0.1 vs. 5.1 ± 0.1).Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 ± 6 vs. 170 ± 4 mmHg, respectively).Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Center, Federal University of Paraíba João Pessoa, Brazil.

ABSTRACT
We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic treatment with HEX on cardiovascular parameters were evaluated. HEX induced endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 ± 4.1%; potency [pD2] = 5.1 ± 0.1). Relaxation was attenuated by scavenging nitric oxide (ME = 44.9 ± 9.4% vs. 100.4 ± 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 ± 9.7% vs. 100.4 ± 4.1%). In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 ± 0.1 vs. 5.1 ± 0.1) or by inhibiting KATP channels (pD2 = 4.3 ± 0.1 vs. 5.1 ± 0.1). HEX increased NO levels in mesenteric arteries (33.2 ± 2.3 vs. 10.7 ± 0.2 au, p < 0.0001). Intravenous acute administration of HEX (1-20 mg/kg) induced hypotension and bradycardia in normotensive and hypertensive rats. Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 ± 6 vs. 170 ± 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive K(+) channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats.

No MeSH data available.


Related in: MedlinePlus