A multitude of G-protein coupled receptors act in the RVLM. GPCRs signal via Gα proteins mainly through three major signaling cascades. We sought to determine the role Gαi/s/AC/cAMP signaling cascades play in the RVLM in the tonic and reflex regulation of arterial pressure (AP). In urethane anaesthetized, paralysed and artificially ventilated rats, activators and inhibitors of PKA (Sp-,Rp-cAMPs) were injected into the RVLM. Activation evoked profound increases in AP (55±13mmHg, 5nmol, n=4) and sympathetic nerve activity (115±19%) and facilitated baroreceptor and somatosympathetic reflex function. In conscious telemetered SHR (n=9) and WKY (n=10) we compared the autonomic responses (MAP, HR and temperature) evoked by 8-OHDPAT (0.1, 1, 3mg/kg iv) or oxotremorine (0.2mg/kg iv). Significantly enhanced dose related responses (AP and/or HR) were evoked in SHR suggesting that the GPCRs or downstream proteins are altered. In SHR, blockade of Gαi/o proteins in the RVLM, using pertussis toxin (PTX), abolished the cardiovascular effects of 8-OHDPAT and oxotremorine at day 6 but not at day 2 following PTX administration but had no effect on the resting level of AP. These data indicate that in the RVLM, activation of 1) Gs proteins evoke profound sympathoexcitatory effects and enhanced sympathetic reflex function and 2) Gi proteins evoke enhanced responses in SHR versus WKY but may play little role in setting the level of AP.
|Issue number||Suppl. 1|
|Publication status||Published - 1 Apr 2009|