Limits...
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

Representative tracings from a sham operated rat illustrating changes in pulse arterial pressure (PAP, mmHg), mean arterial pressure (MAP, mmHg), and heart rate (HR, bpm) in response to administration of HEX (1; 5; 10; and 20 mg/kg).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4553900&req=5

Figure 5: Representative tracings from a sham operated rat illustrating changes in pulse arterial pressure (PAP, mmHg), mean arterial pressure (MAP, mmHg), and heart rate (HR, bpm) in response to administration of HEX (1; 5; 10; and 20 mg/kg).

Mentions: Six weeks after 2K1C surgery, the baseline MAP was increased compared with sham-operated rats (145 ± 3 vs. 120 ± 2 mmHg, respectively, n = 6, p < 0.05). A representative tracing from a sham operated rat is shown in Figure 5. In normotensive rats, HEX (1; 5; 10; and 20 mg/kg) reduced blood pressure (−20 ± 6; −32 ± 5; −57 ± 9; −76 ± 9 mmHg) followed by a slight tachycardia in first two doses (8 ± 2 and 14 ± 6 bpm) and significant bradycardia in last two doses (−68 ± 20 and −206±34 bpm) as shown in Figures 6A,B. Furthermore, in conscious hypertensive rats, HEX (1; 5; 10; and 20 mg/kg) reduced blood pressure in a dose-dependent fashion (−9 ± 5; −12 ± 3; −15 ± 6; −79 ± 10 mmHg, respectively), also followed by bradycardia (−15 ± 3; −8 ± 26; −15 ± 18 and −355±29 bpm) as shown in Figures 6C,D.


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)

Representative tracings from a sham operated rat illustrating changes in pulse arterial pressure (PAP, mmHg), mean arterial pressure (MAP, mmHg), and heart rate (HR, bpm) in response to administration of HEX (1; 5; 10; and 20 mg/kg).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Representative tracings from a sham operated rat illustrating changes in pulse arterial pressure (PAP, mmHg), mean arterial pressure (MAP, mmHg), and heart rate (HR, bpm) in response to administration of HEX (1; 5; 10; and 20 mg/kg).
Mentions: Six weeks after 2K1C surgery, the baseline MAP was increased compared with sham-operated rats (145 ± 3 vs. 120 ± 2 mmHg, respectively, n = 6, p < 0.05). A representative tracing from a sham operated rat is shown in Figure 5. In normotensive rats, HEX (1; 5; 10; and 20 mg/kg) reduced blood pressure (−20 ± 6; −32 ± 5; −57 ± 9; −76 ± 9 mmHg) followed by a slight tachycardia in first two doses (8 ± 2 and 14 ± 6 bpm) and significant bradycardia in last two doses (−68 ± 20 and −206±34 bpm) as shown in Figures 6A,B. Furthermore, in conscious hypertensive rats, HEX (1; 5; 10; and 20 mg/kg) reduced blood pressure in a dose-dependent fashion (−9 ± 5; −12 ± 3; −15 ± 6; −79 ± 10 mmHg, respectively), also followed by bradycardia (−15 ± 3; −8 ± 26; −15 ± 18 and −355±29 bpm) as shown in Figures 6C,D.

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