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After chronic (2-6 wk) sinoaortic deafferentation (SAD), rats exhibit slight increases in mean arterial pressure (MAP) and heart rate and marked increases in arterial pressure lability. Neither antagonists of humoral vasoconstrictors angiotensin and vasopressin nor acute hypophysectomy altered MAP or lability after chronic SAD. Ganglionic blockade produced hypotension and significantly reduced lability in SAD rats but decreased MAP and increased lability in normal rats. Although chlorisondamine reduced lability in rats with SAD to levels observed in similarly treated sham-operated rats, lability was significantly greater in both groups than in saline-treated sham-operated rats. When intact or SAD rats were administered chlorisondamine plus either captopril or a vasopressin antagonist, pressure lability was returned to levels seen in intact untreated animals. Selective antagonism of alpha 1- or alpha 2-adrenergic receptors did not markedly alter lability in SAD rats. Combined alpha-adrenergic blockade reduced lability in SAD rats and increased lability in intact rats, similar to chlorisondamine treatment. These data suggest that chronic SAD establishes arterial pressure variability that is maintained or generated in large part by the sympathetic nervous system through mechanisms dependent on higher central structures or descending efferent sympathetic nerves. The data further suggest that peripheral mechanisms may also be involved in arterial pressure regulation in baroreceptor-deficient rats.

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Previously our laboratory has shown that 17β-estradiol in vivo rapidly decreases R(+)-8-OH-DPAT-stimulated [³⁵S]GTPγS binding (a measure of the initial biochemical event in the intracellular signaling pathway associated with 5-HT_1A receptors) in the hippocampus, frontal cortex and amygdala. Studies were designed to determine if 17β-estradiol also acts in vitro on estrogen receptors in the hippocampus and frontal cortex to decrease 5-HT_1A receptor function. Hippocampus and frontal cortex were dissected from ovariectomized rats and incubated for up to 3 h with various estrogens and antiestrogens; membrane homogenates were prepared for R(+)-8-OH-DPAT-stimulated [³⁵S]GTPγS binding assays. 17β-Estradiol (10^–6 M) decreased the maximal response in the R(+)-8-OH-DPAT-stimulated [³⁵S]GTPγS binding assay in a time-dependent manner (observed at 30, 60 and 120 min) in both hippocampus and frontal cortex. The hormone, however, did not alter the EC₅₀ of R(+)-8-OH-DPAT. When hippocampus and frontal cortex were incubated in graded concentrations of 17β-estradiol for 1 h, the calculated EC₅₀ was approximately 2.5 × 10^–8 M in both brain regions. The nonestradiol estrogen diethylstilbestrol also decreased 5-HT_1A receptor function while the less potent estrogens 17α-estradiol and estriol were inactive at 5 × 10^–8 M. The estrogen receptor antagonist ICI 182,780 potently and completely blocked the effects of 17β-estradiol on 5-HT_1A receptor function with an apparent K_B of approximately 10^–9 M. These data demonstrate clearly that estrogens can act on estrogen receptors located in hippocampus and frontal cortex of ovariectomized rats to produce rapid heterologous decreases in 5-HT_1A receptor function.

Serotonin (5-HT) and 5-HT agonists act on multiple 5-HT receptor subtypes to increase corticosterone secretion. The present experiments describe the effects of a highly selective 5-HT₂ receptor agonist DOI [(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1] on plasma corticosterone in conscious, unrestrained, male rats with indwelling arterial and venous catheters. DOI (500 µg/kg, i.v.) increased plasma corticosterone levels 6- to 7-fold from 15 to 60 min. Pretreatment with the central 5-HT₂ antagonist LY 53857 (100 µg/kg, i.v.) blocked the effect of DOI on corticosterone secretion at all times. The peripheral 5-HT₂ antagonist xylamidine (100 µg/kg, i.v.) attenuated the corticosterone response elicited 15 min after DOI but did not alter the 60-min response. In contrast, dexamethasone pretreatment (350 µg/kg, s.c.) attenuated the corticosterone response to DOI at 15 min, but abolished the response at 60 min. The increase in corticosterone levels elicited 5 min after the nonselective 5-HT agonist quipazine (3 mg/kg, i.v.) was also reduced by xylamidine. These data suggest that 5-HT₂ receptor agonists increase corticosterone secretion initially, in part, through a direct adrenal mechanism not entirely dependent on adrenocorticotropin, and at later times via a central, dexamethasone-suppressible mechanism. This raises the possibility that endogenous 5-HT in the adrenal medulla may act as a local paracrine to participate in the regulation of corticosterone secretion from the adrenal cortex.