The antihypertensive property of NIP-121, a novel potassium channel opener in rats.

Abstract

The antihypertensive effects of NIP-121, a novel potassium channel opener, were examined in comparison with cromakalim and its active enantiomer, lemakalim. In experiments by direct blood pressure measurements, orally administered NIP-121 dose-relatedly decreased arterial blood pressure in conscious spontaneously hypertensive rats (SHRs), and the ED20 values (the doses to produce 20% decrease of the mean blood pressure) of NIP-121 and cromakalim were 0.010 and 0.11 mg/kg, respectively, NIP-121 thus being about ten times more potent than cromakalim. The duration of the hypotensive effect by NIP-121 was longer than that by cromakalim. The hypotensive effect of NIP-121 was stronger in SHRs than in normotensive rats. All three drugs showed tachycardia that was antagonized by a beta-blocker, propranolol. Intravenously administered NIP-121 also showed a more potent hypotensive action with longer duration than cromakalim in conscious SHRs. The ED20 values for hypotension by NIP-121, cromakalim, and lemakalim were 0.017, 0.040, and 0.016 mg/kg, respectively. The intravenous hypotensive potency of NIP-121 but not cromakalim was similar to that of p.o. administration. The repeated treatments with NIP-121 (0.025, 0.05, and 0.1 mg/kg p.o. once a day) for 15 days did not modify the degree of the hypotensive action. In the anesthetized SHRs, pretreatment with glibenclamide but not other antagonists (atropine, propranolol, diphenhydramine + cimetidine, or indomethacin) suppressed the decrease in blood pressure induced by NIP-121.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: Y Masuda, C Arakawa, T Yokoyama, K Shigenobu, S Tanaka
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 18 Issue 2 Pg. 190-7 (Aug 1991) ISSN: 0160-2446 [Print] United States
• PMID: 1717778 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antihypertensive Agents
• Benzopyrans
• Oxadiazoles
• Piperidines
• Potassium Channels
• Pyrroles
• Cromakalim
• NIP 121

Topics

• Administration, Oral
• Animals
• Antihypertensive Agents (pharmacology)
• Benzopyrans (pharmacology)
• Blood Pressure (drug effects)
• Cromakalim
• Dose-Response Relationship, Drug
• Heart Rate (drug effects)
• Injections, Intravenous
• Male
• Oxadiazoles (pharmacology)
• Piperidines (pharmacology)
• Potassium Channels (drug effects)
• Pyrroles (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred Strains
• Rats, Inbred WKY
• Species Specificity