Blunted fenfluramine-evoked prolactin secretion in hypertensive rats.
Plasma prolactin (PRL) levels after acute administration of fenfluramine (FEN) have been used as a probe of brain serotonin activity. FEN-evoked increases in PRL levels inversely correlate with arterial blood pressure (ABP) in humans (Muldoon et al. Hypertension. 1998;32:972-975), thereby suggesting that brain serotonin activity may be reduced in hypertension. The present study sought to determine whether the relation between FEN-evoked PRL levels and ABP was present in two rat models of hypertension. Experiments were performed in awake male rats that were instrumented with femoral arterial and venous catheters 2 days before experiments. FEN (3.0 mg/kg IV) significantly increased plasma PRL levels in both spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY); however, FEN-evoked PRL levels were significantly lower in SHR compared with WKY, though baseline levels were similar between strains. Similar results were obtained in rats with chronic hypertension produced by figure-8 renal wrap plus contralateral nephrectomy. In contrast, the increase in PRL levels evoked by the serotonin receptor agonist m-CPP or the dopamine receptor antagonist eticlopride did not differ between SHR and WKY, indicating that PRL secretion is not generally blunted in chronic hypertensive rats. Furthermore, FEN-evoked PRL levels were not attenuated in rats made acutely hypertensive by an infusion of the alpha-adrenergic agonist phenylephrine. Thus, the present findings are consistent with the human data and suggest that chronic hypertension is associated with a presynaptic alteration in brain serotonin function.
Stocker
Sean D
SD
Department of Neuroscience, University of Pittsburgh, 446 Crawford Hall, Pittsburgh, Penn 15260, USA.
Muldoon
Matthew F
MF
Sved
Alan F
AF
D000208:Acute Disease; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002908:Chronic Disease; D005277:Fenfluramine / Q000494:pharmacology*; D006973:Hypertension / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D006977:Hypertension, Renal / Q000097:blood / Q000503:physiopathology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011388:Prolactin / Q000097:blood* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D018490:Serotonin Agents / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D018490:Serotonin Agents; D010656:Phenylephrine; D005277:Fenfluramine; D011388:Prolactin