Hemin blunts the depressant effect of chronic nicotine on reflex tachycardia via activation of central NOS/PI3K pathway in female rats
| Autor: | Mahmoud M. El-Mas, Hanan M. El-Gowelli, Mohamed A. Fouda, Sahar M. El-Gowilly |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Nitroprusside
0301 basic medicine Nicotine medicine.medical_specialty Baroreceptor Blood Pressure Baroreflex Arginine 03 medical and health sciences chemistry.chemical_compound Soluble Guanylyl Cyclase 0302 clinical medicine Tachycardia Internal medicine medicine Animals Rats Wistar Pharmacology biology Chemistry Estrogens General Medicine Rats Androstadienes Heme oxygenase Nitric oxide synthase NG-Nitroarginine Methyl Ester 030104 developmental biology Endocrinology Heme Oxygenase (Decyclizing) Reflex biology.protein Hemin Female Sodium nitroprusside Mitogen-Activated Protein Kinases Nitric Oxide Synthase Phosphatidylinositol 3-Kinase Wortmannin 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Pharmacological Reports. 70:455-462 |
| ISSN: | 1734-1140 |
| DOI: | 10.1016/j.pharep.2017.09.008 |
| Popis: | Chronic nicotine administration impairs reflex chronotropic responses that follow arterial baroreceptor unloading in female rats with repleted, but not depleted (ovariectomized, OVX), estrogen (E2). This study investigated whether products of nitric oxide synthase (NOS) and/or heme oxygenase (HO) and related soluble guanylate cyclase (sGC)/phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinases (MAPKs) signaling mediate the E2-sensitive depressant effect of nicotine on reflex tachycardia. Baroreflex curves relating reflex tachycardic responses to falls in blood pressure (BP) generated by sodium nitroprusside (SNP) were established in conscious female rats and slopes of the curves were taken as measures of baroreflex sensitivity (BRS). Nicotine (2 mg/kg/day ip, 14 days) reduced BRS in OVX rats treated with E2 but not vehicle. Baroreceptor dysfunction in nicotine-treated OVXE2 rats was abolished after iv treatment with hemin (HO inducer) but not l-arginine (NOS substrate) denoting the importance of reduced availability of carbon monoxide, but not NO, in the nicotine effect. The favorable BRS effect of hemin was abolished after intracisternal (ic) administration of L-NAME (NOS inhibitor) or wortmannin (PI3 K inhibitor). Central circuits of MAPKs do not seem to contribute to the baroreflex facilitatory effect of hemin because the latter was preserved after central inhibition of MAPKERK (PD98059), MAPKp38 (SB203580) or MAPKJNK (SP600125). Likewise, sGC inhibition (ODQ) or E2 receptor blockade (ICI182780) failed to alter the hemin effect. The activation of central NOS/PI3K signaling following HO upregulation improves the E2-dependent depressant effect of nicotine on reflex tachycardia. |
| Databáze: | OpenAIRE |
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