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NO production in rabbit aorta rings
230
Pharmacological
Research, Vol. 26, Supplement 1, 1992
NITRIC OXIDE SYNTHESIS AND HISTAMINE RELEASE IN ISOtATED MAST CELLS AND HEART FROM SPONTANEOUSLY HYPERTENSIVE RATS: INFLUENCE OF AGING. Gambassi F., Lupini M., Mugnai L., Mannaioni P.F. and Masini E. Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy. Rat serosal mast cells (MC) isolated from Wistar Albino rats synthesize a nitric oxide (NO)-like factor which inhibits platelet aggregation and stimulates guanylate cyclase, playing an important role in the regulation of histamine and free radical release. An impairement of the L-arginine-NO-pathway in MC isolated from spontaneously hypertensive (SH) rats has been shown recently. Here we demonstrate that in isolated perfused heart and in serosal MC isolated from peritoneal and pleural washing of 2-, 6- and 18-month old SH rats (systolic blood pressure 185 k3.8 mm Hg) the production of NO is significantly less than in in MC and in the heart of normotensive Wistar Kyoto (WKY) rats of the same age. Concomitantly, basal and ischaemic-reperfusion evoked histamine release and MC reactivity to various exocytotic stimuli (compound 48/80, calcium ionophore A 23187) is modified by aging and hypertension. The production of NO-like factor in isolated MC is assessed by two bioassays: inhibition of platelet aggregation and stimulation of MC guanylate cyclase; in cardiac perfusates it is assessed by measuring nitrite production, as final product of Larginine-NO-biosynthesis, by the Griess reaction. Histamine release is determined fluorimetrically. These results suggest that NO synthesis and/or release from cardiac and serosal MC is involved in the events associated with aging and hypertension.
EFFECT OF PRODUCTS OF PROTEIC CATABOLISM
ON EDRF/NO PRODUCTION
IN RABBIT AORTA RINGS Sorrentino, L. Sorrentino and A. Pinto Dept. of Experimental Pharmacology, University of Naples "Federico II" Nitric oxide (NO) that accounts for EDRF effects, is produced from nitrogen group of L-arginine. The proteic catabolism produces azw&dth variety of substances structurally related to the guanidine. We tested the effect of guanidine, urea, methyl -guanidine, creatinine and guanidinosuccinic acid on rabbit aorta rings relaxation induced by agents acting by receptorial (acetylcholine, ACh) or non-receptorial (A23187) mechanisms. Creatinine (O-1-10 mM) did not modify the relaxation induced by both ACh or A23187. Guanidine and methylguanidine in a concentration-dependent manner (O-1-10 mM) produced inhibition of both ACh- or A23187-induced relaxation. Urea (0.1-100 mM) reduced the relaxation induced by ACh but not the relaxation induced by A23187. In contrast, guanidinosuccinic acid produced a significant (p 0.05) increase of relaxation, probably acting as a L-arginine like substrate. This results indicate that some products of proteic catabolism can reduce NO formation. R.
Pharmacological
Research, Vol. 26, Supplement 1, 1992
NITRIC OXIDE SYNTHESIS AND HISTAMINE RELEASE IN ISOtATED MAST CELLS AND HEART FROM SPONTANEOUSLY HYPERTENSIVE RATS: INFLUENCE OF AGING. Gambassi F., Lupini M., Mugnai L., Mannaioni P.F. and Masini E. Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy. Rat serosal mast cells (MC) isolated from Wistar Albino rats synthesize a nitric oxide (NO)-like factor which inhibits platelet aggregation and stimulates guanylate cyclase, playing an important role in the regulation of histamine and free radical release. An impairement of the L-arginine-NO-pathway in MC isolated from spontaneously hypertensive (SH) rats has been shown recently. Here we demonstrate that in isolated perfused heart and in serosal MC isolated from peritoneal and pleural washing of 2-, 6- and 18-month old SH rats (systolic blood pressure 185 k3.8 mm Hg) the production of NO is significantly less than in in MC and in the heart of normotensive Wistar Kyoto (WKY) rats of the same age. Concomitantly, basal and ischaemic-reperfusion evoked histamine release and MC reactivity to various exocytotic stimuli (compound 48/80, calcium ionophore A 23187) is modified by aging and hypertension. The production of NO-like factor in isolated MC is assessed by two bioassays: inhibition of platelet aggregation and stimulation of MC guanylate cyclase; in cardiac perfusates it is assessed by measuring nitrite production, as final product of Larginine-NO-biosynthesis, by the Griess reaction. Histamine release is determined fluorimetrically. These results suggest that NO synthesis and/or release from cardiac and serosal MC is involved in the events associated with aging and hypertension.
EFFECT OF PRODUCTS OF PROTEIC CATABOLISM
ON EDRF/NO PRODUCTION
IN RABBIT AORTA RINGS Sorrentino, L. Sorrentino and A. Pinto Dept. of Experimental Pharmacology, University of Naples "Federico II" Nitric oxide (NO) that accounts for EDRF effects, is produced from nitrogen group of L-arginine. The proteic catabolism produces azw&dth variety of substances structurally related to the guanidine. We tested the effect of guanidine, urea, methyl -guanidine, creatinine and guanidinosuccinic acid on rabbit aorta rings relaxation induced by agents acting by receptorial (acetylcholine, ACh) or non-receptorial (A23187) mechanisms. Creatinine (O-1-10 mM) did not modify the relaxation induced by both ACh or A23187. Guanidine and methylguanidine in a concentration-dependent manner (O-1-10 mM) produced inhibition of both ACh- or A23187-induced relaxation. Urea (0.1-100 mM) reduced the relaxation induced by ACh but not the relaxation induced by A23187. In contrast, guanidinosuccinic acid produced a significant (p 0.05) increase of relaxation, probably acting as a L-arginine like substrate. This results indicate that some products of proteic catabolism can reduce NO formation. R.