Biomedical subjects

Erik Uddman

Publications and source records attributed to Erik Uddman.

3 recordsLinked to original sources

PubMed2002

Analysis of the time course for organ culture-induced endothelin ET B receptor upregulation in rat mesenteric arteries.

In contrast to the constitutively expressed endothelin ET(A) receptor, the distribution of endothelin ET(B) receptors is more variable. The aim of the present study was to investigate the kinetics of organ culture-induced upregulation of contractile endothelin ET(B) receptors in rat mesenteric arteries at both mRNA and functional levels. Assessment of mRNA expression revealed low levels of endothelin ET(B) receptor mRNA relative to endothelin ET(A) receptor mRNA after 3 h of culture, which gradually increased to reach a plateau level after 24 h. Correspondingly, vessels cultured for 3 h showed a negligible contractile response the selective endothelin ET(B) receptor agonist sarafotoxin 6c. Subsequently, the contractile response to sarafotoxin 6c was successively increased during organ culture until 24 h and, thereafter, a further increase in potency was seen after 48 h. These results demonstrate a rapid induction of transcription within less than 7 h followed by an increase in the response to receptor stimulation.

Animals↗

PubMed2002

Protein kinase C inhibitors decrease endothelin ET(B) receptor mRNA expression and contraction during organ culture of rat mesenteric artery.

The effect of protein kinase C (PKC) inhibitors on the induction of endothelin ET(B) receptors during organ culture was examined in isolated segments of the rat mesenteric artery. After 24 h of organ culture, the endothelin ET(B) receptor agonist sarafotoxin 6c (S6c) induced a strong contraction compared to fresh segments. The contractile response after 24-h organ culture to S6c was studied in presence (30-min preincubation) or absence, after 24-h treatment, of the PKC inhibitors staurosporine, K252a and Ro31-7549. Exposure to staurosporine or K252a in presence and after 24-h treatment reduced the S6c contraction. In contrast, presence of 2-1[1-3(aminopropyl)indol-3-yl]-3(1-methyl-1H-indol-3-yl)maleimide (Ro31-7549), did not affect the S6c-induced contraction, whereas 24-h treatment abolished the increase of contraction. The PKA inhibitor N-(2-[bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H89) did not affect the S6c responses. The mRNA expressions of endothelin ET(B) receptors (analysed with real-time PCR) were abolished after 24-h treatment with the PKC inhibitors. These results suggest that PKC is involved in the endothelin ET(B) receptor upregulation following organ culture.

Animals↗

PubMed2002

Cerebral ischemia upregulates vascular endothelin ET(B) receptors in rat.

BACKGROUND AND PURPOSE: Elevated levels of endothelin-1 (ET-1) have been reported in cerebral ischemia. A role for ET may prove more important if the vascular receptors were changed. We addressed whether there is any change in ET receptor expression in cerebral ischemia. METHODS: The right middle cerebral artery (MCA) was occluded in male Wistar rats for 2 hours with the intraluminal filament method. The basilar artery and both MCAs were removed after 46 hours of recirculation. The contractile responses to ET-1, a combined ET(A) and ET(B) receptor agonist, and sarafotoxin 6c (S6c), a selective ET(B) receptor agonist, were examined in vitro, and ET receptor mRNA was quantified by real-time polymerase chain reaction. RESULTS: S6c, which had no contractile effect per se on fresh or sham-operated rat cerebral arteries, induced a marked contraction in the occluded MCA (E(max) [maximum contraction, calculated as percentage of the contractile capacity of 63.5 mmol/L K+]=68+/-68%; P<0.0001), while there was no difference in the responses to ET-1 after cerebral ischemia. Real-time polymerase chain reaction revealed a significant upregulation of both the ET(A) and ET(B) receptors (both P<0.05) in the occluded MCA compared with the nonoccluded MCA from the same rats. CONCLUSIONS: Focal cerebral ischemia in rat induces increased transcription of both ET(A) and ET(B) receptors, which results in the appearance of a contractile response to the ET(B) receptor agonist S6c. These results suggest a role for ET receptors in the pathogenesis of a vascular component after cerebral ischemia.

Animals↗