BRAIN ANGIOTENSIN-II RECEPTOR SUBTYPES AND THE CONTROL OF LUTEINIZING-HORMONE AND PROLACTIN SECRETION IN FEMALE RATS

The present experiments examined the role of the two recently identified angiotensin II (Ang II) receptor subtypes, AT1 and AT2, in the central nervous system regulation of luteinizing hormone (LH) and prolactin secretion in estrogen- and progesterone-treated ovariectomized rats. In this animal model, intracerebroventricular (icv) injection of Ang II stimulates LH and inhibits prolactin release. The specific Ang II receptor subtype antagonists losartan (AT1) or PD123177 (AT2) were administered (icv) in various doses (10 ng to 1,000 ng) 10 min prior to icv injection of Ang II (100 ng). Control animals were pretreated with artificial cerebrospinal fluid prior to Ang II administration. Blood samples for LH and prolactin determinations were taken from conscious, freely-moving rats prior to and following injection of the antagonists and Ang II. Water intake was measured. Ang II-induced water intake was attenuated 62% by 1,000 ng losartan; water intake was not affected by lower doses of losartan or by any dose of PD123177. Ang II-induced stimulation of LH release was abolished by the 1,000 ng doses of losartan and PD123177 and attenuated by the 500 ng doses of both drugs. Lower doses did not affect Ang II-induced LH secretion. Ang II-induced inhibition of prolactin release was significantly reduced by the 1,000 ng doses of both losartan and PD123177. Lower doses ot either drug did not affect the Ang II inhibition ot prolactin release. Previous studies had shown that Ang II administration into the anterior hypothalamus-medial preoptic (AHPO) area stimulated LH release. This brain area contains AT1 receptors. To investigate the potential brain site where the AT2 receptor may influence LH release, Ang II was injected into the locus ceruleus, a brain nucleus which contains predominately the AT2 receptor subtype. Ang II administration into the locus ceruleus was paired with an injection of artificial cerebrospinal fluid or Ang II into the AHPO area. Injection of Ang II into the AHPO area stimulated LH release. Injection into the locus ceruleus did not affect LH secretion, nor did it modify the rise in LH elicited by administration of Ang II into the AHPO area. Plasma levels of prolactin were not altered by any of these injections. Taken together, these data demonstrate that, in estrogen- and progesterone-treated female rats, icv Ang II-induced water intake is mediated by the AT1 receptor subtype, while Ang II-induced changes in LH and prolactin secretion appear to be mediated by both the AT1 and AT2 receptor subtypes. The latter observations are one of the first suggesting a potential function for the AT2 subtype in vivo, although the physiological relevance of this observation, as well as the site of action for the effects on LH and prolactin, remain to be established.