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CARDIOVASCULAR

Role of Nitric Oxide in -Melanocyte-Stimulating Hormone-Induced Hypotension in the Nucleus Tractus Solitarii of the Spontaneously Hypertensive Rats

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (M.-H.T., W.-T.W., W.-C.L., J.Y.H.C., C.-J.L., H.-C.L., C.-J.T.); Graduate Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (M.-H.T.); and Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (W.-T.W., C.-J.T.)

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 -melanocyte-stimulating hormone (-MSH), a POMC-derived neuropeptide, and its relationship with NO pathway in the NTS of spontaneously hypertensive rats (SHR). Unilateral microinjection of -MSH (0.3–300 pmol) into the NTS resulted in a dose-dependent hypotension and bradycardia in urethane-anesthetized SHR. The -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 -MSH. To elucidate the role of NO pathway in -MSH-evoked hypotension, pretreatment with N-nitro-L-arginine methyl ester, a universal inhibitor of nitric-oxide synthase (NOS), partially reversed the depressor and bradycardic effects of -MSH. Furthermore, previous application of the inducible NOS (iNOS) inhibitor, aminoguanidine, but not the neuronal NOS inhibitor, 7-nitroindazole, attenuated the cardiovascular effect of -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 -MSH induces hypotension and bradycardia of SHR via MC-4R signaling, which activates cAMP/PKA and iNOS.

Address correspondence to: Dr. Ching-Jiunn Tseng, Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung 813, Taiwan. E-mail: cjtseng{at}vghks.gov.tw

This article has been cited by other articles:

				A. A. da Silva, J. M. do Carmo, B. Kanyicska, J. Dubinion, E. Brandon, and J. E. Hall Endogenous Melanocortin System Activity Contributes to the Elevated Arterial Pressure in Spontaneously Hypertensive Rats Hypertension, April 1, 2008; 51(4): 884 - 890. [Abstract] [Full Text] [PDF]