Nitric oxide, a possible mediator of 1,4-dihydropyridine-induced photorelaxation of vascular smooth muscle

Fina Lovren, Sean K. O'Neill, Detlef Bieger, Nadeem Igbal, Ed E. Knaus, Christopher Triggle

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

1. In rat aortic tissues pre-contracted with phenylephrine, certain 1,4-dihydropyridines (DHPs) such as Bay K 8644 (0.1 μM), PN 20,2791 (1 μM), RK 30 (1 μM), NI 104 (1 μM) and NI 105 (1 μM) enhanced photoactivated relaxations (photorelaxation or PR) whereas NI 72, NI 85, NI 99, NI 102, amlodipine, felodipine, nifedipine and nimodipine were inactive. 2. The PR inducing effects of Bay K 8644 were mimicked by the diabetogenic agent, streptozotocin (STZ). 3. Solutions of Bay K 8644 which had been irradiated for various periods of time initiated light independent transient relaxations followed by contractile responses in aortic tissue partially contracted with phenylephrine. With exposure times to light of 30 to 120 min, the intensity of the relaxation response to irradiated Bay K 8644 increased from 26 ± 3.3 to 71 ± 3.7% of the maximum contractile response to phenylephrine (n = 5). Conversely the contractile responses decreased, from 84.2 ± 4.1 to 19.8 ± 10.4% of the maximum contractile response to phenylephrine (n = 5). 4. Superoxide ions, generated by incubation of xanthine (2 mM) plus xanthine oxidase (10 mu ml-1) in physiological saline solution (PSS) NaCl 118, KCl 4.7, CaCl2 2.5, KH2PO4 1.2, MgSO4 1.2, NaHCO3 12.5 and glucose 11.1 (mM) for 1 h, reduced the PR induced by DHPs, STZ, and also NO-induced relaxations of rat aortic preparations. 5. Direct measurements of NO indicate that, following exposure to a polychromatic light source, equimolar concentrations (O.1 mM) of the DHP compounds that enhance PR, as well as STZ, photodegrade to release NO (25 ± 2-40.3 ± 5.9 nmol min-1, n = 6). 6. Structure-activity studies indicate that a nitro group at the -3 position of the dihydropyridine ring is essential for DHPs to support PR. 7. These data suggest that the photodegradation of DHPs and STZ leading to the release of NO provides the primary cellular process underlying the PR response.

Original languageEnglish
Pages (from-to)879-884
Number of pages6
JournalBritish Journal of Pharmacology
Volume118
Issue number4
Publication statusPublished - 1996
Externally publishedYes

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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Dihydropyridines
Phenylephrine
Streptozocin
Vascular Smooth Muscle
Nitric Oxide
Light
Felodipine
Amlodipine
Nimodipine
Xanthine
Xanthine Oxidase
Photolysis
Nifedipine
Sodium Chloride
Superoxides
Ions
Glucose
1,4-dihydropyridine

Keywords

  • Chemiluminescence
  • Dihydropyridines (DHPs)
  • Nitric oxide
  • Photorelaxation
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Pharmacology

Cite this

Nitric oxide, a possible mediator of 1,4-dihydropyridine-induced photorelaxation of vascular smooth muscle. / Lovren, Fina; O'Neill, Sean K.; Bieger, Detlef; Igbal, Nadeem; Knaus, Ed E.; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 118, No. 4, 1996, p. 879-884.

Research output: Contribution to journalArticle

Lovren, Fina ; O'Neill, Sean K. ; Bieger, Detlef ; Igbal, Nadeem ; Knaus, Ed E. ; Triggle, Christopher. / Nitric oxide, a possible mediator of 1,4-dihydropyridine-induced photorelaxation of vascular smooth muscle. In: British Journal of Pharmacology. 1996 ; Vol. 118, No. 4. pp. 879-884.
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T1 - Nitric oxide, a possible mediator of 1,4-dihydropyridine-induced photorelaxation of vascular smooth muscle

AU - Lovren, Fina

AU - O'Neill, Sean K.

AU - Bieger, Detlef

AU - Igbal, Nadeem

AU - Knaus, Ed E.

AU - Triggle, Christopher

PY - 1996

Y1 - 1996

N2 - 1. In rat aortic tissues pre-contracted with phenylephrine, certain 1,4-dihydropyridines (DHPs) such as Bay K 8644 (0.1 μM), PN 20,2791 (1 μM), RK 30 (1 μM), NI 104 (1 μM) and NI 105 (1 μM) enhanced photoactivated relaxations (photorelaxation or PR) whereas NI 72, NI 85, NI 99, NI 102, amlodipine, felodipine, nifedipine and nimodipine were inactive. 2. The PR inducing effects of Bay K 8644 were mimicked by the diabetogenic agent, streptozotocin (STZ). 3. Solutions of Bay K 8644 which had been irradiated for various periods of time initiated light independent transient relaxations followed by contractile responses in aortic tissue partially contracted with phenylephrine. With exposure times to light of 30 to 120 min, the intensity of the relaxation response to irradiated Bay K 8644 increased from 26 ± 3.3 to 71 ± 3.7% of the maximum contractile response to phenylephrine (n = 5). Conversely the contractile responses decreased, from 84.2 ± 4.1 to 19.8 ± 10.4% of the maximum contractile response to phenylephrine (n = 5). 4. Superoxide ions, generated by incubation of xanthine (2 mM) plus xanthine oxidase (10 mu ml-1) in physiological saline solution (PSS) NaCl 118, KCl 4.7, CaCl2 2.5, KH2PO4 1.2, MgSO4 1.2, NaHCO3 12.5 and glucose 11.1 (mM) for 1 h, reduced the PR induced by DHPs, STZ, and also NO-induced relaxations of rat aortic preparations. 5. Direct measurements of NO indicate that, following exposure to a polychromatic light source, equimolar concentrations (O.1 mM) of the DHP compounds that enhance PR, as well as STZ, photodegrade to release NO (25 ± 2-40.3 ± 5.9 nmol min-1, n = 6). 6. Structure-activity studies indicate that a nitro group at the -3 position of the dihydropyridine ring is essential for DHPs to support PR. 7. These data suggest that the photodegradation of DHPs and STZ leading to the release of NO provides the primary cellular process underlying the PR response.

AB - 1. In rat aortic tissues pre-contracted with phenylephrine, certain 1,4-dihydropyridines (DHPs) such as Bay K 8644 (0.1 μM), PN 20,2791 (1 μM), RK 30 (1 μM), NI 104 (1 μM) and NI 105 (1 μM) enhanced photoactivated relaxations (photorelaxation or PR) whereas NI 72, NI 85, NI 99, NI 102, amlodipine, felodipine, nifedipine and nimodipine were inactive. 2. The PR inducing effects of Bay K 8644 were mimicked by the diabetogenic agent, streptozotocin (STZ). 3. Solutions of Bay K 8644 which had been irradiated for various periods of time initiated light independent transient relaxations followed by contractile responses in aortic tissue partially contracted with phenylephrine. With exposure times to light of 30 to 120 min, the intensity of the relaxation response to irradiated Bay K 8644 increased from 26 ± 3.3 to 71 ± 3.7% of the maximum contractile response to phenylephrine (n = 5). Conversely the contractile responses decreased, from 84.2 ± 4.1 to 19.8 ± 10.4% of the maximum contractile response to phenylephrine (n = 5). 4. Superoxide ions, generated by incubation of xanthine (2 mM) plus xanthine oxidase (10 mu ml-1) in physiological saline solution (PSS) NaCl 118, KCl 4.7, CaCl2 2.5, KH2PO4 1.2, MgSO4 1.2, NaHCO3 12.5 and glucose 11.1 (mM) for 1 h, reduced the PR induced by DHPs, STZ, and also NO-induced relaxations of rat aortic preparations. 5. Direct measurements of NO indicate that, following exposure to a polychromatic light source, equimolar concentrations (O.1 mM) of the DHP compounds that enhance PR, as well as STZ, photodegrade to release NO (25 ± 2-40.3 ± 5.9 nmol min-1, n = 6). 6. Structure-activity studies indicate that a nitro group at the -3 position of the dihydropyridine ring is essential for DHPs to support PR. 7. These data suggest that the photodegradation of DHPs and STZ leading to the release of NO provides the primary cellular process underlying the PR response.

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KW - Dihydropyridines (DHPs)

KW - Nitric oxide

KW - Photorelaxation

KW - Vascular smooth muscle

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