Expression of Inositol 1,4,5-trisphosphate Receptor mRNA in Myocardium of Spontaneous Hypertension Rats and Cultured Vascular Smooth Muscle Cells of Rats

Objective\ To investigate expression of inositol 1,4,5 trisphosphate receptor (IP\-3R) mRNA on sacroplasmic reticular in myocardium of spontaneous hypertension rats (SHRs) and cultured vascular smooth muscle cells (VSMC) of rats and effects of perindopril and urapidil on them. Methods\ SHRs were orally given perindopril (1.0 mg·kg\+\{ 1\}·d\+\{ 1\}) or urapidil (15 mg·kg\+\{ 1\}·d\+\{ 1\}) for 24 weeks, respectively. Expression of IP\-3R mRNA was examined by semi quantitative reverse transcription polymers chain reaction (RT PCR) using three oligonuclotide primers for each subtype of IP\-3R with β actin as internal label. Results\ All subtypes of IP\-3R were expressed in myocardium of SHR, WKY and cultured VSMC. Expression of IP\-3R mRNA in left ventricle of SHR was markedly enhanced. Urapidil could down regulate expression of IP\-3R Ⅰand IP\-3R Ⅲ, perindopril slightly increased expression of IP\-3R Ⅱ and decreased expression of IP\-3R Ⅰand IP\-3R Ⅲ in myocardium of SHR. Conclusion\ Our results suggest that expression of IP\-3R mRNA in cardiovascular system could be regulated by urapidil and perindopril.

Calcium signaling in cholangiocytes

Cytosolic Ca^2＋ is an important second messenger in virtually every type of cell. Moreover, Ca^2＋ generally regulates multiple activities within individual cells. This article reviews the cellular machinery that is responsible for Ca^2＋ signaling in cholangiocytes. In addition, two Ca^2＋-mediated events in cholangiocytes are discussed： bicarbonate secretion and apoptosis. Finally, emerging evidence is reviewed that Ca^2＋ signaling is involved in the pathogenesis of diseases affecting the biliary tree and that Ca^2＋ signaling pathways can be manipulated to therapeutic advantage in the treatment of cholestatic disorders.

Vascular contractile response and signal transduction in endothelium-denuded aorta from cirrhotic rats

AIM: The mechanism of decreased vascular reactivity to vasoconstrictors in portal hypertension is still unclear. In addition to nitric oxide, defects in post-receptor signal transduction pathway have been suggested to play a role.However, substantial evidences observed equivocal changes of vascular reactivity following different agonists that challenged the hypothesis of the post-receptor defect. The current study was to evaluate the vascular reactivity to different agonists and the inositol trisphosphate (IP3)changes in signal transduction cascade from cirrhotic rats with portal hypertension.METHODS: The endothelial denuded aortic rings from cirrhotic and sham-operated rats were obtained for ex vivo tension study and measurement of the corresponding [3H] IP3 formation following different receptor and nonreceptor-mediated agonists' stimulation. Additionally,iNOS protein expression was measured in thoracic aorta.The contractile response curves to phenylephrine were performed in endothelial denuded aortic rings with and without preincubation with a specific iNOS inhibitor (L-N (6)-(1-iminoethyl)-lysine, L-NIL).RESULTS: In endothelial denuded aortic rings of cirrhotic rats, the vascular responses were reduced with phenylephrine and arginine vasopressin (AVP) stimulation but were normal with U-46619, NaF/AlCl3, and phorbol esterdibutyrate (PdBU) stimulation. Compared to the corresponding control groups, the degree of the increment of [3H] IP3 formation from basal level was also decreased with phenylephrine and AVP stimulation, but was normal with U-46619 and NaF/AlCl3 stimulation. The preincubation with L-NIL did not modify the hyporesponsiveness to phenylephrine. Additionally, the iNOS protein expression in thoracic aorta was not different in cirrhotic and shamoperated rats.CONCLUSION: Without the influence of nitric oxide, vascular hyporeactivity to vasoconstrictors persisted in cirrhotic rats with portal hypertension. However, the decreased vascular reactivity is an agonist-specific phenomenon. In addition,G-protein and phospholipase C pathway associated with the IP3 productions may be intact in cirrhotic rats with portal hypertension.