Role of group 1 metabotropic glutamate receptors (mGluR) in the hypothalamic paraventricular nucleus (PVN) in sympathetic and blood pressure control during water deprivation

Abstract

Compared to WKY rats, sympathetic nerve activity (SNA) and elevated arterial pressure (AP) in spontaneous hypertensive rats (SHR) is supported by enhanced glutamatergic drive of group 1 mGluR (mGluR1 & mGluR5) in the PVN. Whether enhanced group 1 mGluR activity is a genetically determined feature of sympathetic control unique to SHR or is a mechanism of PVN activation common to other hypertensive states is undetermined. To investigate this, euhydrated (EU) and 48 h water deprived (WD) rats were studied, as dehydration also acutely increases AP by increasing glutamatergic drive of the PVN. In conscious EU rats, injection of the group 1 mGluR agonist DHPG (2 nmol in 200 nl) increased AP (n=3, p<0.05). This effect was attenuated by prior PVN injection of the mGluR1 antagonist LY‐367385 (4 nmol in 200 nl; n=3, p<0.05), but not the mGluR5 antagonist MPEP (4 nmol in 200 nl; n=2). Injections of LY and MPEP alone were each without affect in EU (n=2) and WD rats (n=3). Similar results were obtained in EU (n=3) and WD (n=2) rats under anesthesia in which renal SNA was also unaffected by blockade of PVN group 1 mGluR. Thus, whereas activation of PVN group 1 mGluR is sympathoexcitatory and contributes to sympathetic support of ongoing AP in SHR, the latter appears not to be a common mechanism of PVN driven support of SNA or elevated AP, as no tonic role for PVN group 1 mGluR activity was observed either in EU or 48 h WD rats. HL102310 and HL088052 (GMT)