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The loss of blood plasma volume (induction of hypovolemia) by either administration of polyethylene glycol or water deprivation is known to stimulate the increase of angiotensin II in plasma and to induce drinking (Kutscher, 1968; Malvin et al., 1977; Vijande et al., 1978; Mann et al., 1980; Johnson et al., 1981; Yamaguchi et al., 1982).

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European Journal of PharmacoloD', 109 (1985) 249-256Elsevier249INCREASE OF P L A S M A R E N I N ACTIVITY AFTER S U B C U T A N E O U S A P P L I C A T I O N OFC O M P O U N D 4 8 / 8 0 IN THE RATHIROSHI IZUMI *, SIU-CHEONGHO *, ANDREW M. MICHELAKIS* and TSUYOSHI AOKIDepartment of Physiology, Tohoku Unit,ersi(t' School of Dentisto', Seio'o-Machi 4-1, Sendai 980, Japan, and * Department ofPharmacology and Toxicology, Michigan State Unit,ersitv, East Lansing, Michigan 48824, U.S.A.Received 13 June 1984. revised MS received 1 November 1984, accepted 27 November 1984H. IZUMI, S.-C. HO, A.M. MICHELAKIS and T. AOKI, Increase of plasma renin activity after subcutaneousapplication of compound 4 8 / 8 0 in the rat, European J. Pharmacol. 109 (1985) 249-256.Subcutaneous (s.c.) administration of compound 48/80 (3.0 mg/kg) to conscious rats produced a time-dependentlong-lasting increase of plasma renin activity (PRA). A dose-related increase of the hematocrit was also observed afterinjection of compound 48/80. The onset of the hematocrit increase preceded that of PRA increase. Pretreatment witha dose of more than 20 mg/kg of histamine HI-receptor antagonists such as tripelennamine or diphenhydramine priorto the injection of compound 48/80 (3.0 mg/kg s.c.) attenuated or abolished the effects of compound 48/80 on PRA,hematocrit and plasma extravasation. Pretreatment with cimetidine (histamine H2-receptor antagonist, 40 mg/kg i.p.)had no effect on these plasma variables

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