Role of paraventricular nucleus vasopressin V1A receptors in the response to endothelin 1 activation of the subfornical organ in the rat.
Endothelin (ET) acts at selected brain loci to elicit a pressor response and vasopressin (AVP) secretion. The pressor action of centrally acting ET is mediated via enhanced efferent sympathetic nerve activity. ET-induced VP secretion depends upon the ET receptor subtype and the brain region involved. ET(A)R activation at the subfornical organ (SFO) increases mean arterial pressure and renal sympathetic nerve activity (RSNA) as well as AVP secretion in awake rats. These effects are only partly mediated by glutamatergic receptors in paraventricular nucleus (PVN). Recent data indicate dendritic release of AVP may act as a neurotransmitter. We therefore hypothesized that dendritic release of AVP from magnocellular PVN neurons contributes to the increase in arterial pressure and RSNA due to ET(A) receptor activation at SFO. Male Sprague Dawley rats equipped with vascular catheters, renal nerve electrodes, and intracerebral cannulae directed into SFO and magnocellular PVN bilaterally were studied 48hr after recovery in the awake state. Hemodynamic and neural parameters were monitored continuously. Microinjection of 5 pmol ET1 into SFO increased mean arterial pressure by 15.8 +/- 4.2 mmHg accompanied by reflex decreases in heart rate and RSNA. Microinjection of 100 ng of the V(1a) receptor antagonist alone bilaterally into the PVN did not change baseline parameters; however, the pressor response to ET1 was significantly attenuated with mean arterial pressure increasing only by 6.1 +/- 3.0 mmHg (P<0.05). Reflex changes in heart rate and RSNA did not change. These findings support the concept that dendritic release of VP from magnocellular neurons within the PVN mediates, at least in part, the pressor response to ET(A) receptor activation at the SFO.
Rossi
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NF
Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. nrossi@med.wayne.edu
Maliszewska-Scislo
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M
D000818:Animals; D001794:Blood Pressure; D003712:Dendrites / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D006339:Heart Rate; D007668:Kidney / Q000294:innervation; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism*; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism*
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D017483:Receptors, Vasopressin; D014667:Vasopressins