A possible correlation between the correction of endothelial dysfunction and normalization of high blood pressure levels by 1,3,4-oxadiazole derivative, an L-type Ca2+ channel blocker in deoxycorticosterone acetate and NG-nitro-l-arginine hypertensive rats

G.R. Bankar, G.K. Nampurath, P.G. Nayak, S. Bhattacharya

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Abstract

We have previously demonstrated the vasorelaxant activity of 1,3,4-oxadiazole derivative (NOX-1) through L-type Ca2+ channel blockage. In the present study, we investigated whether the correction of endothelial dysfunction is dependent on the normalization of high blood pressure levels by 1,3,4-oxadiazole derivative (NOX-1) in deoxycorticosterone acetate (DOCA-salt) and NG-nitro-l-arginine (L-NNA) hypertensive rats. In DOCA-salt and L-NNA hypertensive rats, the mean systolic blood pressure (MSBB) was 185.3 ± 4.7 and 170.2 ± 4.1 mmHg, whereas after administration of NOX-1 to hypertensive rats, MSBB was 127.8 ± 4.5 and 120.2 ± 5.1 mmHg, respectively. To study the endothelial dysfunction, concentration-response curves of norepinephrine (NE) and acetylcholine (Ach) were constructed in rat aortic rings isolated from normotensive, hypertensive (DOCA and L-NNA) and NOX-1 treated rats. NE-induced contractions and Ach-induced relaxations were significantly (p < 0.05) decreased and increased, respectively in the aorta of NOX-1 treated rats. Vasorelaxant activity of NOX-1 was not abolished by pretreatment of aortic rings with L-NNA, 1H-[1,2,4] oxadiazolo [4,3-A] quinoxalin-1-one (ODQ), indomethacin or glibenclamide. The results suggest that the endothelial dysfunction can be corrected by the L-type Ca2+ channel blocker with endothelium-independent action and that is dependent on the normalization of high blood pressure levels. The antihypertensive and vasorelaxant effects of NOX-1 are mainly endothelial-independent and it can be used to treat hypertension, a state associated with endothelial dysfunction. © 2009 Elsevier Ireland Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)327-331
Number of pages5
JournalChemico-Biological Interactions
Volume183
Issue number2
DOIs
Publication statusPublished - 2010

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Desoxycorticosterone Acetate
Desoxycorticosterone
Blood pressure
Arginine
Rats
Acetates
Hypertension
Derivatives
Salts
Vasodilator Agents
Acetylcholine
Norepinephrine
Blood Pressure
Quinoxalines
Glyburide
Ireland
Indomethacin
Antihypertensive Agents
Endothelium
Aorta

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@article{065df93f81774e8589f0ad41b77768ea,
title = "A possible correlation between the correction of endothelial dysfunction and normalization of high blood pressure levels by 1,3,4-oxadiazole derivative, an L-type Ca2+ channel blocker in deoxycorticosterone acetate and NG-nitro-l-arginine hypertensive rats",
abstract = "We have previously demonstrated the vasorelaxant activity of 1,3,4-oxadiazole derivative (NOX-1) through L-type Ca2+ channel blockage. In the present study, we investigated whether the correction of endothelial dysfunction is dependent on the normalization of high blood pressure levels by 1,3,4-oxadiazole derivative (NOX-1) in deoxycorticosterone acetate (DOCA-salt) and NG-nitro-l-arginine (L-NNA) hypertensive rats. In DOCA-salt and L-NNA hypertensive rats, the mean systolic blood pressure (MSBB) was 185.3 ± 4.7 and 170.2 ± 4.1 mmHg, whereas after administration of NOX-1 to hypertensive rats, MSBB was 127.8 ± 4.5 and 120.2 ± 5.1 mmHg, respectively. To study the endothelial dysfunction, concentration-response curves of norepinephrine (NE) and acetylcholine (Ach) were constructed in rat aortic rings isolated from normotensive, hypertensive (DOCA and L-NNA) and NOX-1 treated rats. NE-induced contractions and Ach-induced relaxations were significantly (p < 0.05) decreased and increased, respectively in the aorta of NOX-1 treated rats. Vasorelaxant activity of NOX-1 was not abolished by pretreatment of aortic rings with L-NNA, 1H-[1,2,4] oxadiazolo [4,3-A] quinoxalin-1-one (ODQ), indomethacin or glibenclamide. The results suggest that the endothelial dysfunction can be corrected by the L-type Ca2+ channel blocker with endothelium-independent action and that is dependent on the normalization of high blood pressure levels. The antihypertensive and vasorelaxant effects of NOX-1 are mainly endothelial-independent and it can be used to treat hypertension, a state associated with endothelial dysfunction. {\circledC} 2009 Elsevier Ireland Ltd. All rights reserved.",
author = "G.R. Bankar and G.K. Nampurath and P.G. Nayak and S. Bhattacharya",
note = "Cited By :17 Export Date: 10 November 2017 CODEN: CBINA Correspondence Address: Bankar, G.R.; Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Madhav Nagar, Manipal, 576104 Karnataka, India; email: garry_scop999@yahoo.co.in Chemicals/CAS: 1h 1,2,4 oxadiazolo[4,3 a]quinoxalin 1 one, 41443-28-1; acetylcholine, 51-84-3, 60-31-1, 66-23-9; deoxycorticosterone acetate, 56-47-3; glibenclamide, 10238-21-8; indometacin, 53-86-1, 74252-25-8, 7681-54-1; n(g) nitroarginine, 2149-70-4; nifedipine, 21829-25-4; noradrenalin, 1407-84-7, 51-41-2; 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 4-(3-acetyl-5-(pyridine-3-yl)-2,3-dihydro-1,3,4-oxadiazole-2-yl)phenyl acetate; Antihypertensive Agents; Calcium Channel Blockers; Calcium Channels, L-Type; Desoxycorticosterone, 64-85-7; Enzyme Inhibitors; Glyburide, 10238-21-8; Indomethacin, 53-86-1; Nitroarginine, 2149-70-4; Norepinephrine, 51-41-2; Oxadiazoles; Quinoxalines; Vasodilator Agents Tradenames: nox 1 References: Yanagisawa, M., Kuruhara, H., Kimura, S., Mitsui, Y., Kobayashi, M., Watanabe, T.X., Masaki, T., A novel potent vasoconstrictor peptide produced by vascular endothelial cells (1998) Nature, 332, pp. 411-415; Vanhoutte, P.M., Other endothelium derived relaxation factors (1992) Circulation, 87, pp. V9-V17; Panza, J.A., Quyyumi, A.A., Brush, J.E., Abnormal endothelium dependent vascular relaxation in patients with essential hypertension (1990) N. Engl. J. Med., 323, pp. 22-37; Taddei, S., Virdis, A., Mattei, P., Salvetti, A., Vasodilation to acetylcholine in primary and secondary forms of human hypertension (1993) Hypertension, 21, pp. 929-933; Luscher, T.F., Diederich, D., Weber, E., Vanhoutte, P.M., Buhler, F.R., Endothelium-dependent responses in carotid and renal arteries of normotensive and hypertensive rats (1988) Hypertension, 11, pp. 573-578; Paniagua, O.A., Bryant, M.B., Panza, J.A., Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature: diminished activity in hypertensive and hypercholesterolemic patients (2001) Circulation, 103, pp. 1752-1758; Carvalho, M.H.C., Fortes, Z.B., Nigro, D., Oliveira, M.A., Scivoletto, R., The role of thromboxane A2 in the altered microvascular reactivity in two-kidney, one-clip hypertension (1997) Endothelium, 5, pp. 167-178; Shirasaki, Y., Su, C., Lee, T.J.F., Kolm, P., Kline, W.H.J.R., Nickols, G., Endothelial modulation of vascular relaxation to nitrovasodilators in aging and hypertension (1986) J. Pharmacol. Exp. Ther., 239, pp. 861-866; Cordellini, S., Carvalho, M.H.C., Scivoletto, R., Fortes, Z.B., Nigro, D., Indirect evidence for an endothelium-derived contracting factor release in aorta of deoxycorticosterone acetate-salt hypertensive rats (1990) J. Hypertens., 8, pp. 53-60; Schiffrin, E.L., Deng, L.Y., Comparison of effects of angiotensin converting enzyme inhibition and β blockade for 2 years on function of arteries from hypertensive patients (1995) Hypertension, 25, pp. 699-703; Schiffrin, E.L., Deng, L.Y., Structure and function of resistance arteries of hypertensive patients treated with a β-blocker or a calcium channel antagonist (1996) J. Hypertens., 14, pp. 1247-1255; Cuman, R.K.N., Nigro, D., Carvalho, M.H.C., Scivoletto, R., Fortes, Z.B., Influence of hydralazine treatment on the vascular reactivity of DOCA-salt hypertensive rats (1994) Endothelium, 2, pp. 105-111; Sharma, A.K., Srinivasan, B.P., Triple verses glimepiride plus metformin therapy on cardiovascular risk biomarkers and diabetic cardiomyopathy in insulin resistance type 2 diabetes mellitus rats (2009) Eur. J. Pharm. Sci., 38, pp. 433-444; Budriesi, R., Cosimelli, B., Cardiovascular characterization of [1,4]thiazino[3,4-c][1,2,4]oxadiazol-1-one derivatives: selective myocardial calcium channel modulators (2002) J. Med. Chem., 45, pp. 3475-3481; Budriesi, R., Cosimelli, B., L-type calcium channel blockers: from diltiazem to 1,2,4-oxadiazol-5-ones via thiazinooxadiazol-3-one derivatives (2009) J. Med. Chem., 52, pp. 2352-2362; Bankar, G.R., Nandakumar, K., Nayak, P.G., Thakur, A., Chamallamudi, M.R., Nampurath, G.K., Vasorelaxant effect in rat aortic rings through calcium channel blockage: a preliminary in vitro assessment of a 1,3,4-oxadiazole derivative (2009) Chem. Biol. Int., 181, pp. 377-382; Bockman, C.S., Jeffries, W.B., Pettinger, W.A., Abel, P.W., Enhanced release of endothelium-derived relaxing factor in mineralocorticoid hypertension (1992) Hypertension, 20, pp. 304-313; Cocks, T.M., Endothelium dependent vasodilator mechanisms (1996) Pharmacology of Vascular Smooth Muscle, pp. 233-251. , Garland C.J., and Angus J.A. (Eds), Oxford University Press, New York, NY; Nelson, M.T., Quayle, J.M., Physiological roles and properties of potassium channels in arterial smooth muscle (1995) Am. J. Physiol., 268, pp. 799-822",
year = "2010",
doi = "10.1016/j.cbi.2009.11.001",
language = "English",
volume = "183",
pages = "327--331",
journal = "Chemico-Biological Interactions",
issn = "0009-2797",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - A possible correlation between the correction of endothelial dysfunction and normalization of high blood pressure levels by 1,3,4-oxadiazole derivative, an L-type Ca2+ channel blocker in deoxycorticosterone acetate and NG-nitro-l-arginine hypertensive rats

AU - Bankar, G.R.

AU - Nampurath, G.K.

AU - Nayak, P.G.

AU - Bhattacharya, S.

N1 - Cited By :17 Export Date: 10 November 2017 CODEN: CBINA Correspondence Address: Bankar, G.R.; Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Madhav Nagar, Manipal, 576104 Karnataka, India; email: garry_scop999@yahoo.co.in Chemicals/CAS: 1h 1,2,4 oxadiazolo[4,3 a]quinoxalin 1 one, 41443-28-1; acetylcholine, 51-84-3, 60-31-1, 66-23-9; deoxycorticosterone acetate, 56-47-3; glibenclamide, 10238-21-8; indometacin, 53-86-1, 74252-25-8, 7681-54-1; n(g) nitroarginine, 2149-70-4; nifedipine, 21829-25-4; noradrenalin, 1407-84-7, 51-41-2; 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 4-(3-acetyl-5-(pyridine-3-yl)-2,3-dihydro-1,3,4-oxadiazole-2-yl)phenyl acetate; Antihypertensive Agents; Calcium Channel Blockers; Calcium Channels, L-Type; Desoxycorticosterone, 64-85-7; Enzyme Inhibitors; Glyburide, 10238-21-8; Indomethacin, 53-86-1; Nitroarginine, 2149-70-4; Norepinephrine, 51-41-2; Oxadiazoles; Quinoxalines; Vasodilator Agents Tradenames: nox 1 References: Yanagisawa, M., Kuruhara, H., Kimura, S., Mitsui, Y., Kobayashi, M., Watanabe, T.X., Masaki, T., A novel potent vasoconstrictor peptide produced by vascular endothelial cells (1998) Nature, 332, pp. 411-415; Vanhoutte, P.M., Other endothelium derived relaxation factors (1992) Circulation, 87, pp. V9-V17; Panza, J.A., Quyyumi, A.A., Brush, J.E., Abnormal endothelium dependent vascular relaxation in patients with essential hypertension (1990) N. Engl. J. Med., 323, pp. 22-37; Taddei, S., Virdis, A., Mattei, P., Salvetti, A., Vasodilation to acetylcholine in primary and secondary forms of human hypertension (1993) Hypertension, 21, pp. 929-933; Luscher, T.F., Diederich, D., Weber, E., Vanhoutte, P.M., Buhler, F.R., Endothelium-dependent responses in carotid and renal arteries of normotensive and hypertensive rats (1988) Hypertension, 11, pp. 573-578; Paniagua, O.A., Bryant, M.B., Panza, J.A., Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature: diminished activity in hypertensive and hypercholesterolemic patients (2001) Circulation, 103, pp. 1752-1758; Carvalho, M.H.C., Fortes, Z.B., Nigro, D., Oliveira, M.A., Scivoletto, R., The role of thromboxane A2 in the altered microvascular reactivity in two-kidney, one-clip hypertension (1997) Endothelium, 5, pp. 167-178; Shirasaki, Y., Su, C., Lee, T.J.F., Kolm, P., Kline, W.H.J.R., Nickols, G., Endothelial modulation of vascular relaxation to nitrovasodilators in aging and hypertension (1986) J. Pharmacol. Exp. Ther., 239, pp. 861-866; Cordellini, S., Carvalho, M.H.C., Scivoletto, R., Fortes, Z.B., Nigro, D., Indirect evidence for an endothelium-derived contracting factor release in aorta of deoxycorticosterone acetate-salt hypertensive rats (1990) J. Hypertens., 8, pp. 53-60; Schiffrin, E.L., Deng, L.Y., Comparison of effects of angiotensin converting enzyme inhibition and β blockade for 2 years on function of arteries from hypertensive patients (1995) Hypertension, 25, pp. 699-703; Schiffrin, E.L., Deng, L.Y., Structure and function of resistance arteries of hypertensive patients treated with a β-blocker or a calcium channel antagonist (1996) J. Hypertens., 14, pp. 1247-1255; Cuman, R.K.N., Nigro, D., Carvalho, M.H.C., Scivoletto, R., Fortes, Z.B., Influence of hydralazine treatment on the vascular reactivity of DOCA-salt hypertensive rats (1994) Endothelium, 2, pp. 105-111; Sharma, A.K., Srinivasan, B.P., Triple verses glimepiride plus metformin therapy on cardiovascular risk biomarkers and diabetic cardiomyopathy in insulin resistance type 2 diabetes mellitus rats (2009) Eur. J. Pharm. Sci., 38, pp. 433-444; Budriesi, R., Cosimelli, B., Cardiovascular characterization of [1,4]thiazino[3,4-c][1,2,4]oxadiazol-1-one derivatives: selective myocardial calcium channel modulators (2002) J. Med. Chem., 45, pp. 3475-3481; Budriesi, R., Cosimelli, B., L-type calcium channel blockers: from diltiazem to 1,2,4-oxadiazol-5-ones via thiazinooxadiazol-3-one derivatives (2009) J. Med. Chem., 52, pp. 2352-2362; Bankar, G.R., Nandakumar, K., Nayak, P.G., Thakur, A., Chamallamudi, M.R., Nampurath, G.K., Vasorelaxant effect in rat aortic rings through calcium channel blockage: a preliminary in vitro assessment of a 1,3,4-oxadiazole derivative (2009) Chem. Biol. Int., 181, pp. 377-382; Bockman, C.S., Jeffries, W.B., Pettinger, W.A., Abel, P.W., Enhanced release of endothelium-derived relaxing factor in mineralocorticoid hypertension (1992) Hypertension, 20, pp. 304-313; Cocks, T.M., Endothelium dependent vasodilator mechanisms (1996) Pharmacology of Vascular Smooth Muscle, pp. 233-251. , Garland C.J., and Angus J.A. (Eds), Oxford University Press, New York, NY; Nelson, M.T., Quayle, J.M., Physiological roles and properties of potassium channels in arterial smooth muscle (1995) Am. J. Physiol., 268, pp. 799-822

PY - 2010

Y1 - 2010

N2 - We have previously demonstrated the vasorelaxant activity of 1,3,4-oxadiazole derivative (NOX-1) through L-type Ca2+ channel blockage. In the present study, we investigated whether the correction of endothelial dysfunction is dependent on the normalization of high blood pressure levels by 1,3,4-oxadiazole derivative (NOX-1) in deoxycorticosterone acetate (DOCA-salt) and NG-nitro-l-arginine (L-NNA) hypertensive rats. In DOCA-salt and L-NNA hypertensive rats, the mean systolic blood pressure (MSBB) was 185.3 ± 4.7 and 170.2 ± 4.1 mmHg, whereas after administration of NOX-1 to hypertensive rats, MSBB was 127.8 ± 4.5 and 120.2 ± 5.1 mmHg, respectively. To study the endothelial dysfunction, concentration-response curves of norepinephrine (NE) and acetylcholine (Ach) were constructed in rat aortic rings isolated from normotensive, hypertensive (DOCA and L-NNA) and NOX-1 treated rats. NE-induced contractions and Ach-induced relaxations were significantly (p < 0.05) decreased and increased, respectively in the aorta of NOX-1 treated rats. Vasorelaxant activity of NOX-1 was not abolished by pretreatment of aortic rings with L-NNA, 1H-[1,2,4] oxadiazolo [4,3-A] quinoxalin-1-one (ODQ), indomethacin or glibenclamide. The results suggest that the endothelial dysfunction can be corrected by the L-type Ca2+ channel blocker with endothelium-independent action and that is dependent on the normalization of high blood pressure levels. The antihypertensive and vasorelaxant effects of NOX-1 are mainly endothelial-independent and it can be used to treat hypertension, a state associated with endothelial dysfunction. © 2009 Elsevier Ireland Ltd. All rights reserved.

AB - We have previously demonstrated the vasorelaxant activity of 1,3,4-oxadiazole derivative (NOX-1) through L-type Ca2+ channel blockage. In the present study, we investigated whether the correction of endothelial dysfunction is dependent on the normalization of high blood pressure levels by 1,3,4-oxadiazole derivative (NOX-1) in deoxycorticosterone acetate (DOCA-salt) and NG-nitro-l-arginine (L-NNA) hypertensive rats. In DOCA-salt and L-NNA hypertensive rats, the mean systolic blood pressure (MSBB) was 185.3 ± 4.7 and 170.2 ± 4.1 mmHg, whereas after administration of NOX-1 to hypertensive rats, MSBB was 127.8 ± 4.5 and 120.2 ± 5.1 mmHg, respectively. To study the endothelial dysfunction, concentration-response curves of norepinephrine (NE) and acetylcholine (Ach) were constructed in rat aortic rings isolated from normotensive, hypertensive (DOCA and L-NNA) and NOX-1 treated rats. NE-induced contractions and Ach-induced relaxations were significantly (p < 0.05) decreased and increased, respectively in the aorta of NOX-1 treated rats. Vasorelaxant activity of NOX-1 was not abolished by pretreatment of aortic rings with L-NNA, 1H-[1,2,4] oxadiazolo [4,3-A] quinoxalin-1-one (ODQ), indomethacin or glibenclamide. The results suggest that the endothelial dysfunction can be corrected by the L-type Ca2+ channel blocker with endothelium-independent action and that is dependent on the normalization of high blood pressure levels. The antihypertensive and vasorelaxant effects of NOX-1 are mainly endothelial-independent and it can be used to treat hypertension, a state associated with endothelial dysfunction. © 2009 Elsevier Ireland Ltd. All rights reserved.

U2 - 10.1016/j.cbi.2009.11.001

DO - 10.1016/j.cbi.2009.11.001

M3 - Article

VL - 183

SP - 327

EP - 331

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

SN - 0009-2797

IS - 2

ER -