Comparison of responses to novel nitric oxide donors in the feline pulmonary vascular bed.
Pulmonary vascular responses to the novel diazeniumdiolate nitric oxide (NO) donors diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt, were investigated and compared in the intact-chest cat. Under conditions of controlled blood flow, when tone in the pulmonary vascular bed had been raised to a high steady level, intralobar injections of diethylamine/NO (0.3-10 microg), diethylenetriamine/NO (10-30 microg), spermine/NO (10-30 microg), sulfite/NO (10-30 microg), and angeli's salt (10-30 microg) caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. In terms of relative vasodilator activity in the pulmonary vascular bed, the dose of the compounds that decreased lobar arterial pressure 4 mm Hg (ED(4) mm Hg) was significantly lower for diethylamine/NO compared to S-nitroso-N-acetylpenicillamine which was significantly less than diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt. The half-life of the vasodilator responses, as measured by 50% response recovery time, to diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt was similar for doses with similar magnitudes of vasodilation, while the half-life to S-nitroso-N-acetylpenicillamine was significantly less than the diazeniumdiolate NO donors. The present data demonstrate that the diazeniumdiolate NO donors diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt have potent but relatively short-lasting vasodilator activity in the pulmonary vascular bed of the cat.
De Witt
B J
BJ
Department of Pharmacology SL83, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Marrone
J R
JR
Kaye
A D
AD
Keefer
L K
LK
Kadowitz
P J
PJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004048:Diethylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013447:Sulfites / Q000494:pharmacology
D004048:Diethylamines; D020030:Nitric Oxide Donors; D009573:Nitrites; D011073:Polyamines; D013447:Sulfites; C005391:diethylenetriamine; C021229:oxyhyponitrite; D013096:Spermine; D026423:S-Nitroso-N-Acetylpenicillamine; C034281:diethylamine