Objectives To further invest- igate the molecular mechanism of vasoprotective role of dehydroepiandrosterone (DHEA), we examined DHEA on AT1 receptor and ICAM-1 gene expression in vascular smooth muscle cells (VSMCs)....Objectives To further invest- igate the molecular mechanism of vasoprotective role of dehydroepiandrosterone (DHEA), we examined DHEA on AT1 receptor and ICAM-1 gene expression in vascular smooth muscle cells (VSMCs). Methods RT-PCR and Western Blot was used to determine the change of the expressions of mRNA and protein of AT1 and ICAM- 1 when given various concentration dehydroepian- drosterone. Results 1.AT1 was abundant under the basal condition. The expression of AT1 mRNA and protein decreased after stimulated by DHEA (at 10- 10mol/L , 10-8 mol/L, 10-6 mol/L) , and the effects of DHEA on AT1 protein was dose-dependent. ER inhibitor Tamoxifen and AR inhibitor Flutamide enhanced AT1 protein expression, but did not influence the mRNA expression. 2. The exp-ression of ICAM-1 gene was low under the basal condition.It increased when induced by TNF-α,but decreased when induced by DHEA (at 10-10 mol/L, 10-8 mol/L, 10-6 mol/L) , and the effects of DHEA on ICAM-1 gene expression were dose-dependent. Conclusions These findings suggest that DHEA modulates AT1 and inflammatory factor induced ICAM-1 gene expression in VSMC, but further studies are necessary in the mecha-nism of DHEA action.展开更多
Objective: The present study was designed to investigate the effect of microinfusion angiotensin Ⅱ(Ang Ⅱ),Ang Ⅱ type 1(AT_1)receptor antagonist losartan into the rostral ventrolateral medulla(RVLM)on the barorecept...Objective: The present study was designed to investigate the effect of microinfusion angiotensin Ⅱ(Ang Ⅱ),Ang Ⅱ type 1(AT_1)receptor antagonist losartan into the rostral ventrolateral medulla(RVLM)on the baroreceptor reflex sensitivity(BRS)in urethane-anesthetized rats. Methods: Reflex changes in heart rate(HR)were elicited by bolus intravenous injection of phenylephrine before and during RVLM microinfusion of saline(0.5 μl/h),Ang Ⅱ (1.5 nmol/h),losartan(250 nmol/h),and Ang Ⅱ(1.5 nmol/h)pretreated with microinjection of losartan (50 nmol/0.51 μl)into the RVLM.The average ratio between changes in HR in beats per minute(beats·min -1)and changes in mean arterial pressure [MAP,mmHg(1 mmHg=0.133 kPa)] was used as an index of BRS. Results: Ang Ⅱ resulted in a significant decrease in the BRS for reflex bradycardia compared with control(-2.1±0.1 vs-3.9±0.4 beats·min -1·mmHg -1).Microinfusion of losartan had no significant effect on BRS for reflex bradycardia.The effect of Ang Ⅱ was almost completely abolished by pretreatment with microinjection of losartan. Conclusion:These results showed that the exogenous Ang Ⅱ in the RVLM produces inhibitory modulation of BRS,which is mediated by AT_1 receptor.However,AT_1 receptor in the RVLM is not involved in the tonic control of BRS.展开更多
Objective: Angiotensin Ⅱ is a growth-promoting factor for vascular smooth muscle cells in culture andin the intact animal. The biological effects of angiotensin Ⅱ are manifested only by binding to specific receptors...Objective: Angiotensin Ⅱ is a growth-promoting factor for vascular smooth muscle cells in culture andin the intact animal. The biological effects of angiotensin Ⅱ are manifested only by binding to specific receptors oncell membranes. In the study, we observed that the effect of rat antisense AT1B gene transfer mediated by adenoviral vector-on neointimal proliferation following rat carotid injury. Methods: Antisense AT1B gene was transductedinto the carotid by adenoviral vector after carotid bal1oon injury and the restenosis model was established in SD rat.We measured neointima/media area ratio in local artery at day 21 after gene transfer. Results: Rat antisense AT1Bgene was successfully transducted into local carotid after the carotid balloon injury. Neointima/media area ratiowas significantly reduced (47 %, P<0. 01) at day 21 after gene transfer compared with the control group. Conclusion: The results suggest it is possible that antisense AT1B gene transfer as a potential therapeutic approach prevent neointimal hyperplasia.展开更多
文摘Objectives To further invest- igate the molecular mechanism of vasoprotective role of dehydroepiandrosterone (DHEA), we examined DHEA on AT1 receptor and ICAM-1 gene expression in vascular smooth muscle cells (VSMCs). Methods RT-PCR and Western Blot was used to determine the change of the expressions of mRNA and protein of AT1 and ICAM- 1 when given various concentration dehydroepian- drosterone. Results 1.AT1 was abundant under the basal condition. The expression of AT1 mRNA and protein decreased after stimulated by DHEA (at 10- 10mol/L , 10-8 mol/L, 10-6 mol/L) , and the effects of DHEA on AT1 protein was dose-dependent. ER inhibitor Tamoxifen and AR inhibitor Flutamide enhanced AT1 protein expression, but did not influence the mRNA expression. 2. The exp-ression of ICAM-1 gene was low under the basal condition.It increased when induced by TNF-α,but decreased when induced by DHEA (at 10-10 mol/L, 10-8 mol/L, 10-6 mol/L) , and the effects of DHEA on ICAM-1 gene expression were dose-dependent. Conclusions These findings suggest that DHEA modulates AT1 and inflammatory factor induced ICAM-1 gene expression in VSMC, but further studies are necessary in the mecha-nism of DHEA action.
文摘Objective: The present study was designed to investigate the effect of microinfusion angiotensin Ⅱ(Ang Ⅱ),Ang Ⅱ type 1(AT_1)receptor antagonist losartan into the rostral ventrolateral medulla(RVLM)on the baroreceptor reflex sensitivity(BRS)in urethane-anesthetized rats. Methods: Reflex changes in heart rate(HR)were elicited by bolus intravenous injection of phenylephrine before and during RVLM microinfusion of saline(0.5 μl/h),Ang Ⅱ (1.5 nmol/h),losartan(250 nmol/h),and Ang Ⅱ(1.5 nmol/h)pretreated with microinjection of losartan (50 nmol/0.51 μl)into the RVLM.The average ratio between changes in HR in beats per minute(beats·min -1)and changes in mean arterial pressure [MAP,mmHg(1 mmHg=0.133 kPa)] was used as an index of BRS. Results: Ang Ⅱ resulted in a significant decrease in the BRS for reflex bradycardia compared with control(-2.1±0.1 vs-3.9±0.4 beats·min -1·mmHg -1).Microinfusion of losartan had no significant effect on BRS for reflex bradycardia.The effect of Ang Ⅱ was almost completely abolished by pretreatment with microinjection of losartan. Conclusion:These results showed that the exogenous Ang Ⅱ in the RVLM produces inhibitory modulation of BRS,which is mediated by AT_1 receptor.However,AT_1 receptor in the RVLM is not involved in the tonic control of BRS.
文摘Objective: Angiotensin Ⅱ is a growth-promoting factor for vascular smooth muscle cells in culture andin the intact animal. The biological effects of angiotensin Ⅱ are manifested only by binding to specific receptors oncell membranes. In the study, we observed that the effect of rat antisense AT1B gene transfer mediated by adenoviral vector-on neointimal proliferation following rat carotid injury. Methods: Antisense AT1B gene was transductedinto the carotid by adenoviral vector after carotid bal1oon injury and the restenosis model was established in SD rat.We measured neointima/media area ratio in local artery at day 21 after gene transfer. Results: Rat antisense AT1Bgene was successfully transducted into local carotid after the carotid balloon injury. Neointima/media area ratiowas significantly reduced (47 %, P<0. 01) at day 21 after gene transfer compared with the control group. Conclusion: The results suggest it is possible that antisense AT1B gene transfer as a potential therapeutic approach prevent neointimal hyperplasia.
