Protective effect of the calcium antagonist NKY-722 against renal and arterial injuries in Dahl salt-sensitive rats.

Abstract

OBJECTIVE:

To study the effect of long-term administration of NKY-722 and nicardipine on renal dysfunction and morphological changes in the kidneys and arteries in Dahl salt-sensitive (Dahl-S) rats.

DESIGN:

Vehicle, NKY-722 and nicardipine were administered orally to Dahl-S rats fed a high-salt diet for 6 weeks.

METHODS:

Systolic blood pressure was measured once a week. At the last week blood and urine were collected and an autopsy was carried out.

RESULTS:

NKY-722 (1 mg/kg per day) lowered blood pressure reproducibly for 6 weeks, whereas nicardipine (3 mg/kg per day) showed a similar effect at week 1 only. NKY-722 tended to decrease blood urea-nitrogen, and reduced plasma creatinine and renin activity significantly. NKY-722 increased urine volume, urinary sodium, creatinine and protein excretions, but did not affect urinary N-acetyl-beta-D-glucosaminidase activity significantly. NKY-722 increased the glomerular filtration rate and reduced glomerulosclerosis and renal arterial injury morphologically. Nicardipine did not affect blood or urinary parameters, but reduced glomerular injury significantly. NKY-722 but not nicardipine reduced cerebral arterial injury. A lower dose of NKY-722 (0.3 mg/kg per day) did not affect blood pressure, blood or urinary parameters, but reduced glomerulosclerosis and renal arterial injury significantly. NKY-722 (1 mg/kg per day) and nicardipine (3 mg/kg per day) increased urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and PGE2. NKY-722 but not nicardipine increased the 6-keto-PGF1 alpha:thromboxane B2 ratio in the thoracic aorta.

CONCLUSIONS:

NKY-722 improved the renal dysfunction, and reduced glomerular, renal and cerebral arterial injuries in Dahl-S rats. The effect of NKY-722 on glomerulosclerosis and arterial injuries is, at least partly, independent of blood pressure, and is probably related to the effect on eicosanoid metabolism.

• Authors: H Shirahase, Y Uehara, K Wada, H Shimaji, T Ishimitsu, Y Hashizume, M Kanda, S Nakamura
• Journal: Journal of hypertension (J Hypertens) Vol. 12 Issue 2 Pg. 137-44 (Feb 1994) ISSN: 0263-6352 [Print] England
• PMID: 8021464 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Dihydropyridines
• NKY 722
• Thromboxane A2
• Nicardipine
• Epoprostenol

Topics

• Animals
• Aorta, Thoracic (drug effects, metabolism)
• Arteries (drug effects, injuries, physiology)
• Blood Pressure (drug effects)
• Calcium Channel Blockers (pharmacology)
• Cerebral Arteries (drug effects, injuries)
• Dihydropyridines (pharmacology)
• Epoprostenol (biosynthesis)
• Hypertension (drug therapy)
• Kidney (drug effects, injuries, physiology)
• Male
• Nicardipine (pharmacology)
• Rats
• Renal Artery (drug effects, injuries)
• Thromboxane A2 (biosynthesis)