|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1992 : ¥1,700,000 (Direct Cost : ¥1,700,000)
To elucidate the roles of interleukin 1 beta(IL-1beta), a cytokine with diverse actions, in the control of the cardiocascular system and body fluid balance, the effects of IL-1beta on drinking behavior, cardiovascular system and renal functions were examined in conscious rats.
(1) Drinking behavior -- IL-1beta (i.p.) attenuated osmotic thirst and spontaneous drinking, while hypovolemic thirst and angiotensin II - induced drinking were not affected. The inhibitory responses were suppressed by pretreatment with indomethacin, a cytooxygenase inhibitor.
(2) Cardiovascular function -- IL-1beta (i.v.and i.c.v.) elicited increases in arterial blood pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA )accompained by an increase in body terperature, which were blocked by pretreatment with indomethacin. The maximum changes in AP, HR and RSNA occurred 10 - 15 min after i.v.injection of IL-1beta (100ng), and 20 - 25 min after i.c.v.injection (5 ng). The activity of the sympathe
tic efferent nerves innervating the interscapular brown adipose tissue (BAT) was also increased by IL-1beta. Intravenous injection of IL-1beta increased plasma nosradrenaline and ACTH concentrations. Thus, IL-1beta produces simultaneously activation of sympathetic outflow and ACTH release.
(3) Renal function --IL-1beta (i.p.) decreased daily urinary sodium and potassium excretion, while urine volume was not affected. The IL-1beta - induced decrease in sodium excretion was abolished in renal denervated rats. Kainic acid was injected into the anterioventral third ventricle (AV3V) region, including the organum vasculosum of the lamina terminalis, to examine whether neurons in the AV3V region are involved in the IL-1beta induced responses. The IL-1beta induced decreases in urinary sodium and potassium excretion were abolished inrats with a kainic acid - induced lesion in the AV3V region, while the suppression in drinking and food intake was attenuated but still persistent. Thus, there appears to be several anatomically distinct sites of action of IL-1beta within the brain, possibly involving different receptor subtypes and mechanisms. Less