Nitric oxide in the adrenergic- and CRH-induced activation of hypothalamic-pituitary-adrenal axis

• Autorzy: Gadek-Michalska A. , Bugajski J.
• Języki publikacji: EN

Abstrakty

EN

In this report we investigated the effect of 7-nitroindazole (7-NI), a specific neuronal inhibitor of nitric oxide synthase (nNOS) and L-NAME, a nonselective NOS inhibitor upon the adrenergic- and CRH-induced stimulation of the hypothalamic-pituitary-adrenal axis in nonanesthetized rast. 7-NI given i.p. and L-NAME administered i.c.v. considerably reduced ACTH and corticosterone secretion induced by phenylephrine (30 µg i.c.v.), an alpha1-adrenergic receptor agonist. These inhibitors also diminished the HPA response to isoprenaline (20 µg i.c.v.), a nonselective ß-adrenergic receptor agonist, and i.c.v. L-NAME significantly lowered the ACTH and corticosterone response to clenbuterol (10 µg i.c.v.), a selective ß2-adrenergic agonist. L-NAME abolished the noradrenaline (NA), an alpha- and ß-receptor agonist-evoked ACTH and corticosterone response, which was reversed by pretreatment with i.p. L-arginine, an endogenous NO substrate. 7-NI abolished the stimulatory action of corticotropin-releasing hormone (CRH 1 µg/kg i.p.) on ACTH but not corticosterone secretion. L-NAME only moderately diminished the CRH-induced ACTH secretion, suggesting that a major part of the CRH-induced HPA axis activation is of neuronal origin. Dihydropyridine, nifedipine, a specific L-type Ca2+ channel blocker, inhibited significantly the CRH-induced ACTH and corticosterone response in rats exposed to 3 days crowding stress but not in rats under basal conditions. This finding indicates the strategic importance of Ca2+ influx into the pituitary corticotrops to meet increased secretory requirement under stressful conditions. Collectively, our results point to complex functional relationship between NO, adrenergic agents CRH and Ca2+ in the regulation of HPA axis activity.

Słowa kluczowe

EN

nifedipine; 7-nitroindazole; social stress; nitric oxide; adrenergic receptor agonist; nitric oxide synthase; hypothalamic-pituitary-adrenal axis

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2008
• Tom: 59
• Numer: 2
• Opis fizyczny: p.365-378,fig.,ref.

Twórcy

autor

Gadek-Michalska A.

• Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland

autor

Bugajski J.