Study on organic nitrates, part VIII. Pharmacological activity and nitric oxide generation capacity of nitrate derivatives of piperazine.
Organic nitrates, derivatives of piperazine, incubated with L-cysteine hydrochloride in phosphate buffer at appropriately high pH and temperature underwent decomposition, releasing nitric oxide (NO). NO generated in this reaction was quantitated by polarographic method using a selective ISO NO sensor. Spontaneously hypertensive rats were used in the tests of hypotensive activity of both investigated organic nitrates and their hydroxyl analogues. The experiments with both groups of compounds were performed under identical conditions. The results of the study demonstrated that the ability of individual compounds to release NO influenced in a different manner their pharmacological activity. Only the compound which released the largest quantity of NO during in vitro tests exhibited in vivo the most prolonged hypotensive effect and significant decrease in all arterial blood pressure parameters.
Korzycka
Lucyna
L
Department of Pharmaceutical Chemistry and Drug Analysis, Medical University of Łódź, Muszyńskiego 1, PL 90-151 Łódź, Poland. korzycka@pharm.am.lodz.pl
Górska
Dorota
D
D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009566:Nitrates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000737:chemistry; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D009566:Nitrates; D020030:Nitric Oxide Donors; D010879:Piperazines; D009569:Nitric Oxide