Abstract
Intrathecal injection of bombesin (BBS) promoted hypertensive and sympathoexcitatory effects in normotensive (NT) rats. However, the involvement of rostral ventrolateral medulla (RVLM) in these responses is still unclear. In the present study, we investigated: (1) the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR); (2) the contribution of RVLM BBS type 1 receptors (BB1) to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v.) were instrumented to record mean arterial pressure (MAP), diaphragm (DIA) motor, and renal sympathetic nerve activity (RSNA). In NT rats and SHR, BBS (0.3 mM) nanoinjected into RVLM increased MAP (33.9 ± 6.6 and 37.1 ± 4.5 mmHg, respectively; p < 0.05) and RSNA (97.8 ± 12.9 and 84.5 ± 18.1%, respectively; p < 0.05). In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7%; p < 0.05). BB1 receptors antagonist (BIM-23127; 3 mM) reduced MAP (–19.9 ± 4.4 mmHg; p < 0.05) and RSNA (−17.7 ± 3.8%; p < 0.05) in SHR, but not in NT rats (−2.5 ± 2.8 mmHg; −2.7 ± 5.6%, respectively). These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.
Highlights
Bombesin (BBS), a tetradecapeptide isolated from the skin of the frog Bombina bombina (Anastasi et al, 1971), have shown broad spectrum of biological activities (Brown, 1983; Gonzalez et al, 2008; Jensen et al, 2008)
The electrophysiological studies have shown that firing rate of Rostral Ventrolateral Medulla (RVLM) neurons is significantly faster in neonatal and adult spontaneously hypertensive rats (SHR) than NT rats (Chan et al, 1991; Matsuura et al, 2002). These findings indicate that hyperactivity of the RVLM neurons could contribute to the development and maintenance of hypertension in SHR
We provided the first evidence that BBS acting in RVLM elicits a significant increase in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) of both NT rats and SHR
Summary
Bombesin (BBS), a tetradecapeptide isolated from the skin of the frog Bombina bombina (Anastasi et al, 1971), have shown broad spectrum of biological activities (Brown, 1983; Gonzalez et al, 2008; Jensen et al, 2008). BBS-like peptides—Neuromedin B (NB) and gastrin releasing peptide (GRP) are natural ligand of the BB1 and BB2 receptors, respectively (Jensen et al, 2008). Natural agonist of the BB3 receptor still remains unknown. It seems that BB3 receptor plays an important physiological role, since BB3 receptor knockout mice developed obesity associated with hypertension and impairment of glucose metabolism (Ohki-Hamazaki et al, 1997). The BB1 receptor signal occurs primarily through phospholipase-C-mediated cascades, that involve activation of Gqα protein and consequent stimulation of protein kinase C (Jensen et al, 2008)
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