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Protective Effects of Iganidipine on Morphological and Functional Changes of Arteries in Hypertensive Dahl Rats

From the Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Kyoto, Japan

Yoshio Uehara

The 2nd Department of Medicine, University of Tokyo, Tokyo, Japan

Mamoru Kanda

From the Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Kyoto, Japan

Katsuo Wada

From the Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Kyoto, Japan

Atsuko Ichikawa

Fuji Biomedix, Yamanashi, Japan

Yoshihiko Kobayashi

Fuji Biomedix, Yamanashi, Japan

Norio Funahashi

Fuji Biomedix, Yamanashi, Japan

Background: This study was performed to examine the protective effects of iganidipine, a new water-soluble calcium antagonist, on the morphological and functional changes of arteries in Dahl salt-sensitive (Dahl-S) rats.

Methods and Results: Vehicle and iganidipine were administered orally to Dahl-S rats fed a high-salt diet (HSD) for 8 weeks. Aorta, superior mesenteric arteries (SMA), and peri pheral mesenteric arteries (PMA) were examined light-microscopically or electron- microscopically. Relaxant responses of isolated aorta and SMA were recorded isometrically. In rats fed HSD, blood pressure was markedly increased. Light microscopy showed intimal and medial hypertrophy, periarteritis, and narrowed arterial lumen in the PMA. Transmis sion and scanning electron microscopy or light microscopy showed medical thickness in the aorta and SMA and hypertrophy of endothelial cells and dilatation of the subendothelial space only in the aorta. In the SMA, both endothelium-dependent relaxation (EDR) and endothelium-independent relaxations (EIR) were reduced to a similar extent. In the aorta, the EDR was more markedly attenuated than the EIR. Iganidipine at 3 mg/kg/day showed a 24-h sustained hypotensive effect and completely prevented the morphological and func tional changes in both arteries. Iganidipine at 1 mg/kg/day, which lowered blood pressure only for several hours, decreased the injuries in PMA and aortic endothelium and moder ately restored the EDR in the aorta. Iganidipine at 0.3 mg/kg/day had no effects.

Conclusions: In Dahl-S rats fed an HSD, iganidipine completely prevented all the changes at a sustained-hypotensive dose and prevented the injuries of PMA and aortic endothelium and the reduction of EDR in the aorta at a nonsustained hypotensive dose. Nonhemody namic effects of iganidipine may be partly involved in its protective effects against arterial injuries.

Key Words: iganidipine • calcium antagonist • aorta • mesenteric artery • endothelium-dependent relaxation (EDR) • endothelium-independent relaxation (EIR) • arterial injury • Dahl-S rat.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 3, No. 2, 143-152 (1998)
DOI: 10.1177/107424849800300207


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