Role of Nitric Oxide in α-Melanocyte-Stimulating Hormone-Induced Hypotension in the Nucleus Tractus Solitarii of the Spontaneously Hypertensive Rats
| Autor: | Ming-Hong Tai, Wen-Tsan Weng, Julie Y. H. Chan, Wan-Chen Lo, Hing-Chung Lam, Che-Jen Lin, Ching-Jiunn Tseng |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Melanocyte-stimulating hormone Microinjections Neuropeptide Blood Pressure Nitric Oxide Nitric oxide chemistry.chemical_compound Cell Line Tumor Rats Inbred SHR Internal medicine Solitary Nucleus medicine Animals Receptor Protein kinase A Microinjection Pharmacology Dose-Response Relationship Drug Chemistry Cyclic AMP-Dependent Protein Kinases Rats NG-Nitroarginine Methyl Ester Endocrinology nervous system alpha-MSH Hypertension Receptor Melanocortin Type 4 Molecular Medicine Melanocortin Signal transduction hormones hormone substitutes and hormone antagonists Signal Transduction circulatory and respiratory physiology |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 321:455-461 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.106.118299 |
| Popis: | Pro-opiomelanocortin (POMC) is expressed in the nucleus tractus solitarii (NTS) of the brainstem, where nitric oxide (NO) plays an important role in cardiovascular regulation. The POMC-derived neuropeptides and their receptors are important regulators of energy homeostasis and cardiovascular functions in the central nervous system. In this study, we investigated the cardiovascular effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a POMC-derived neuropeptide, and its relationship with NO pathway in the NTS of spontaneously hypertensive rats (SHR). Unilateral microinjection of alpha-MSH (0.3-300 pmol) into the NTS resulted in a dose-dependent hypotension and bradycardia in urethane-anesthetized SHR. The alpha-MSH-induced hypotension was abolished by pretreatment with the antagonist of melanocortin-3/4 receptor (MC-3/4R), Ac-Nle-c[Asp-His-D-Nal(2')-Arg-Trp-Lys]-NH2 (SHU9119). Blockade of cAMP/protein kinase A (PKA), the downstream effector of melanocortin receptors, by previous injection of N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89) also ablated the cardiovascular effect of alpha-MSH. To elucidate the role of NO pathway in alpha-MSH-evoked hypotension, pretreatment with Nomega-nitro-L-arginine methyl ester, a universal inhibitor of nitric-oxide synthase (NOS), partially reversed the depressor and bradycardic effects of alpha-MSH. Furthermore, previous application of the inducible NOS (iNOS) inhibitor, aminoguanidine, but not the neuronal NOS inhibitor, 7-nitroindazole, attenuated the cardiovascular effect of alpha-MSH. Histological analysis revealed the colocalization of MC-4R, but not MC-3R, with iNOS in the NTS of SHR. In summary, intra-NTS injection of alpha-MSH induces hypotension and bradycardia of SHR via MC-4R signaling, which activates cAMP/PKA and iNOS. |
| Databáze: | OpenAIRE |
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