Impairment of the L-arginine-nitric oxide pathway in mast cells from spontaneously hypertensive rats.
Serosal mast cells (MC) from 6 month old spontaneously hypertensive rats (SHR) were compared to MC from 6 month old Wistar Kyoto rats (WKYR) for their ability to release nitric oxide (NO). The relationship between histamine release and NO-like activity from these cells was also investigated. MC from SHR released less NO-like factor than MC from WKYR as assessed by the use of platelet aggregation and soluble guanylate cyclase activation as bioassays for NO. Sodium nitroprusside elevated the concentrations of cGMP to a similar extent in MC from SHR or WKYR. No changes in the levels of cAMP were observed. The release of histamine from MC induced by compound 48/80 or the calcium ionophore A23187 was greater in MC from SHR than in MC from WKYR. Thus, MC from SHR show a decreased production of NO-like activity which is reflected by a decreased ability to inhibit platelet aggregation. The decreased production of cGMP in the MC leads to an increased stimulated release of histamine.
Masini
E
E
William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, UK.
Mannaioni
P F
PF
Pistelli
A
A
Salvemini
D
D
Vane
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012016:Reference Values; D013917:Thrombin / Q000494:pharmacology; D019323:omega-N-Methylarginine; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D001120:Arginine; D000242:Cyclic AMP; D013917:Thrombin; D006152:Cyclic GMP