Agents Actions, Special Conference Issue (1992) 0065-4299/92/02C268-04 $1.50 + 0.20/0 9 1992 Birkh/iuser Verlag, Basel Influence of aging on mast cell production of a nitric oxide-like factor: Comparison between normal and hypertensive rats E. Masini 1, A. Pistelli, M. G. Di Bello, S. Raspanti and P. F. Mannaioni Department of Preclinical and Clinical Pharmacology, Viale G. B. Morgagni 65, 50134 Florence, Italy Abstract Rat serosal mast cells (MCs) isolated from Wistar albino rats synthesize a nitric oxide (NO)-like factor which inhibits platelet aggregation, stimulates guanylate cyclase and modulates mast cell histamine release. Aging can affect the ability of MCs to generate and release chemical mediators. The aim of the present study was to evaluate the ability to generate a NO-like factor by MCs isolated from 2, 6 and 18 month old normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats (systolic blood pressure 180+2.5 mmHg) by two bioassays: inhibition of platelet aggregation and stimulation of MC guanylate cyclase. MCs from SH rats produced less NO-like activity than MCs from normotensive WKY rats of the same age. In both strains aging decreased the capacity of MCs to generate the NO-like factor. These results suggest that NO synthesis and/or release from MCs is involved in some events associated with aging and hypertension. Introduction The synthesis of nitric oxide (NO), originally dem- onstrated in vascular endothelial cells [1], is a recently discovered process shown to occur in many other cells including rat serosal mast cells (MCs) [2]. NO, whose synthesis results from the conversion of the terminal guanidino-nitrogen atom(s) of L-arginine (L-Arg) and is prevented by N~-monomethyl-L-arginine (MeArg), causes vascular relaxation, inhibits platelet aggregation and is therefore an important mediator of vessel wall homeostasis [3]. MCs are secretory cells which i Author for correspondence. play an important role in controlling vascular reactivity through the production of vasoactive substances [4]. Decreased endothelium-dependent relaxation in vessels from hypertensive animals has been reported by some authors [5]. This is prob- ably due to decreased production of NO rather than a defect in the guanylate cyclase system leading to vasodilatation, because the relaxation mediated by sodium nitroprusside (NaNp), an endothelium independent agent, is not altered [6]. The aim of the present investigation is to evaluate the production of MC-derived NO-like factor in aging and hypertension using 2, 6 and 18 month old Wistar Kyoto (WKY) and spontaneously hyper- tensive (SH) rats.