Depressor and diuretic effects of imidazoline receptor stimulation in the paraventricular nucleus of the hypothalamus

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Mueller, Heather
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We investigated the response to intracerebroventricular (ICV) moxonidine with the specific purpose of locating a region of the brain responsible for the blood pressure and renal effects, and linking these effects to either the I$\sb1$ imidazoline receptor or the $\alpha\sb2$ adrenergic receptor. Following ICV injection of moxonidine into the left cerebral ventricle of male Sprague-Dawley rats, depressor and diuretic effects were observed. We proposed that the diuretic effect may involve an inhibition of vasopressin. Accordingly, we next investigated the paraventricular nucleus of the hypothalamus (PVN). We hypothesized that the depressor and diuretic responses may be separable in the PVN. While injection of moxonidine into the PVN produced both a depressor and a diuretic effect, only a diuretic effect was observed following the same dose of guanfacine injected into the PVN. We found that moxonidine has a depressor effect that is not separable from the diuretic effect, while guanfacine ($\alpha\sb{\rm 2a}$ agonist) at the same dose is not capable of eliciting a depressor effect. Further to this experiment, we investigated the role of $\gamma$-aminobutyric acid (GABA) in the response to PVN moxonidine. We cannot rule out the role of GABA in the regulation of blood pressure by the PVN. In summary, the PVN may play an important regulatory role in coordinating cardiovascular output. This regulatory pathway may involve adrenergic control of vasopressin release, and imidazoline receptor-mediated blood pressure control, which may be further regulated by GABA. (Abstract shortened by UMI.)