Increase of plasma @entity3449 activity after subcutaneous application of compound 48/80 in the XXXX .

@entity4444 @entity1169 @entity3933 @entity29075 @entity3449 @entity3044 @entity3485 @entity112 @entity35
Subcutaneous (s.c.) administration of compound 48/80 (3.0 mg/kg) to conscious @entity35 produced a time-dependent long-lasting increase of plasma @entity3449 activity (PRA). A dose-related increase of the hematocrit was also observed after injection of compound 48/80. The onset of the hematocrit increase preceded that of PRA increase. Pretreatment with a dose of more than 20 mg/kg of @entity112 H1-receptor antagonists such as @entity29075 or @entity3933 prior to 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 @entity4444 ( @entity112 H2-receptor antagonist, 40 mg/kg i.p.) had no effect on these plasma variables. The increase of PRA caused by s.c. administration of compound 48/80 was not affected by the pretreatment with @entity1169 (beta-adrenoceptor antagonist, 10 mg/kg i.p.), which completely inhibited the @entity3044 (0.5 mg/kg s.c.)-induced PRA increase. Administration of compound 48/80 did not induce a significant PRA increase in the nephrectomized @entity35 although the increase of hematocrit following s.c. administration of compound 48/80 persisted despite the absence of kidneys. S.c. administration of compound 48/80 (3.0 mg/kg) led to a significant decrease of @entity112 content at the site of injection and to a significant increase in plasma @entity112 concentration without affecting arterial blood pressure. The present data suggest that s.c. administration of compound 48/80 stimulates the release of @entity112 from cutaneous mast cells, which cause an increase in vascular permeability to plasma protein via the stimulation of @entity112 H1-receptors, then leads to @entity3485 . The resulting @entity3485 may directly stimulate the juxtraglomerular cells of the kidney to release @entity3449 .
