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01-06-2010 | Original Article

Colforsin-induced vasodilation in chronic hypoxic pulmonary hypertension in rats

Authors: Ayumu Yokochi, Hiroo Itoh, Junko Maruyama, Erquan Zhang, Baohua Jiang, Yoshihide Mitani, Chikuma Hamada, Kazuo Maruyama

Published in: Journal of Anesthesia | Issue 3/2010

Abstract

Purpose

Colforsin, a water-soluble forskolin derivative, directly activates adenylate cyclase and thereby increases the 3′,5′-cyclic adenosine monophosphate (cAMP) level in vascular smooth muscle cells. In this study, we investigated the vasodilatory action of colforsin on structurally remodeled pulmonary arteries from rats with pulmonary hypertension (PH).

Methods

A total of 32 rats were subjected to hypobaric hypoxia (380 mmHg, 10% oxygen) for 10 days to induce chronic hypoxic PH, while 39 rats were kept in room air. Changes in isometric force were recorded in endothelium-intact (+E) and -denuded (−E) pulmonary arteries from the PH and control (non-PH) rats.

Results

Colforsin-induced vasodilation was impaired in both +E and −E arteries from PH rats compared with their respective controls. Endothelial removal did not influence colforsin-induced vasodilation in the arteries from control rats, but attenuated it in arteries from PH rats. The inhibition of nitric oxide (NO) synthase did not influence colforsin-induced vasodilation in +E arteries from controls, but attenuated it in +E arteries from PH rats, shifting its concentration–response curve closer to that of −E arteries from PH rats. Vasodilation induced by 8-bromo-cAMP (a cell-permeable cAMP analog) was also impaired in −E arteries from PH rats, but not in +E arteries from PH rats, compared with their respective controls.

Conclusions

cAMP-mediated vasodilatory responses without β-adrenergic receptor activation are impaired in structurally remodeled pulmonary arteries from PH rats. In these arteries, endothelial cells presumably play a compensatory role against the impaired cAMP-mediated vasodilatory response by releasing NO (and thereby attenuating the impairment). The results suggest that colforsin could be effective in the treatment of PH.

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Title: Colforsin-induced vasodilation in chronic hypoxic pulmonary hypertension in rats
Authors: Ayumu Yokochi
Hiroo Itoh
Junko Maruyama
Erquan Zhang
Baohua Jiang
Yoshihide Mitani
Chikuma Hamada
Kazuo Maruyama
Publication date: 01-06-2010
Publisher: Springer Japan
Published in: Journal of Anesthesia / Issue 3/2010
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-010-0912-7

At a glance: The STEP trials

Springer Medicine

Colforsin-induced vasodilation in chronic hypoxic pulmonary hypertension in rats

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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