Enhanced contractile effect of phorbol dibutyrate in portal veins from hypertensive rats

doi:10.1016/0006-291X(91)90464-I

Biochemical and Biophysical Research Communications

Volume 176, Issue 3, 15 May 1991, Pages 1552-1556

https://doi.org/10.1016/0006-291X(91)90464-I Get rights and content

Abstract

The effects of phorbol 12.13-dibutyrate (PDBu) on portal veins from hypertensive (SHRSP) and normotensive (WKY) rats were examined. PDBu contracted the strips from SHRSP and WKY in a concentration-dependent manner. However, both twitch contraction and tonic contraction of strips in response to PDBu were enhanced in SHRSP. Treatment with staurosporine reduced contractile response to PDBu in strips from SHRSP. It appears that the activity of protein kinase C in vascular smooth muscle is increased in SHRSP.

References (8)

H. Rasmussen et al.
Biochem. Biophys. Res. Comm
(1984)
M.J. Mackay et al.
Biochem. Biophys. Res. Comm
(1987)
K. Kamata et al.
Gen. Pharmacol
(1990)
T. Resink et al.
Biochem. Biophys. Res. Comm
(1988)

There are more references available in the full text version of this article.

Cited by (3)

Adrenoceptors in SHR: Alterations in binding characteristics and intracellular signal transduction pathways
1995, Life Sciences
There is much data on altered adrenoceptor function in the heart, blood vessel and kidney from spontaneously hypertensive rats (SHR). The enhancement of vascular and renal alpha-adrenoceptor Function, I.e. vasoconstriction and retension of water and sodium, may contribute to the development and maintenance of the hypertension, whereas cardiac alpha-adrenoceptor may be of minor physiological significance. Alpha₁-adrenoceptor-mediated signal transduction as a whole is increased in SHR vascular tissues, but the intracellular signaling per receptor in the kidney seems to be decreased despite increased alpha₁-adrenoceptor density. On the other hand, cardiac and vascular beta-adrenoceptor responsiveness is attenuated in SHR. Reduced vasorelaxation medated by beta-adrenoceptors may also contribute to high blood pressure. The impaired cardiovascular beta-adrenoceptor function in SHR does not appear to be necessarily explained by alterations observed at receptor levels. Alterations in signal transduction should be also considered. Limited data on renal beta-adrenoceptor density and its signaling suggest decreased or unaltered cyclic AMP formation per receptor in SHR. We will review alterations in both binding characteristics and each component of intracellular signal transduction pathways in cardiovascular and renal adrenoceptors of SHR.
The relaxant action of jatrophone in rat portal vein. A comparison with protein kinase C inhibitors
1995, Life Sciences
Jatrophone, staurosporine and H-7, caused graded inhibition of rat portal vein contractions induced by phorbol 12-myristate 13-acetate (PMA), noradrenaline, endothelin-1 or KCl, with IC₅₀s of 86 nM, 13 μM, 11 μM and 9 μM, respectively. Jatrophone was equipotent to H-7, but 100 to 500 fold less potent than staurosporine. Jatrophone, H-7 and staurosporine, also dose-dependently inhibited rhythmic contractions of the rat portal-mesenteric vein with IC₅₀s of 15 μM, 9 μM and 75 nM, respectively. Jatrophone, H-7 and staurosporine caused graded relaxations of preparations contracted with endothelin-1 or PMA with IC₅₀s of 12 and > 1000 μM, 8 and 13 μM and 7 and 12 nM, respectively. All three compounds caused graded inhibition of caffeine-induced contractions in Ca -free solution containing EGTA. The similarity between the vasorelaxant actions of Jatrophone, staurosporine and H-7 in rat portal vein suggests that Jatrophone acts, at least in part, through inhibition of PKC-dependent mechanisms. Moreover, like the PKC inhibitors, its vasorelaxant action may also involve other mechanisms unrelated to protein kinase C inhibition.
Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus
1992, Life Sciences
To investigate the influence of diabetes mellitus on the responsiveness of the vascular smooth muscle, the effects of various vasoactive agents on the reactivity of the vascular smooth muscle from diabetic animals have been undertaken, focusing on the functional changes in the endothelium, alpha-adrenoceptors, beta-adrenoceptors, voltage-dependent Ca²⁺-channels, receptor-operated Ca²⁺-channels, phosphatidylinositol turnover and potassium channels. Among the functional changes, it is a common phenomenon that decreases in acetylcholine-induced production of cyclic GMP are due to the attenuation of release of endothelium-derived relaxing factor through an impairment of endothelium; this observation was found in both rats and rabbits with diabetes mellitus. These functional changes in diabetes may be responsible for the vascular complications such as coronary heart disease, cerebrovascular disease, and an accelation in atherosclerosis.

View full text

Enhanced contractile effect of phorbol dibutyrate in portal veins from hypertensive rats

Abstract

Biochem. Biophys. Res. Comm

Biochem. Biophys. Res. Comm

Gen. Pharmacol

Biochem. Biophys. Res. Comm