The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the ...The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.展开更多
Objectives To evaluate the anti- ischemic effect of ISDN on the patients with coronary heart disease . The change in the size of the defect area as percentage of the entire myocardium as determined by the unfolded sur...Objectives To evaluate the anti- ischemic effect of ISDN on the patients with coronary heart disease . The change in the size of the defect area as percentage of the entire myocardium as determined by the unfolded surface mapping between the baseline and after ISDN infusion reflects the anti-ischemic effect of ISDN. Methods and Results 99m Tc-MIBI myocardial perfusion SPECT images were acquired, and reconstruction of the bull's eye map and unfolded surface mapping were performed according to the dates of tomography images. In the group (99mTc-MIBI was injected at 30 minutes after the start of ISDN iv drip) : at the 65% threshold value, the percentage of the defect area size in the whole ventricle was 33.01 ± 5.35% at baseline, (28.9 ±5.23)% after ISDN was infused (P < 0.05); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (22.06±5.58)% at baseline, (19.60±4.07)% after ISDN was infused (P < 0.05); the sum of defect blood ST segments is 60 at baseline, 51 after ISDN was infused. In the group (99mTc-MIBI was injected at 60 minutes after the start of ISDN iv drip): at the 65% threshold value, the percentage of the defect area size in the whole ventricle was (29.20±5.08)% at baseline, (20.81±4.16)% after ISDN was infused (P < 0.001); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (21.2 ± 5.49)% at baseline, (17.52±5.59)% after ISDN was infused (P < 0.001); the sum of defect blood ST segments is 58 at baseline, 47 after ISDN was infused. In the group (99mTc-MIBI was injected at 150 minutes after the start of ISDN iv drip) : at the 65% threshold value, the percentage of the defect area size in the whole ventricle was (32.87 ±6.46)% at baseline, (20.81±4.16)% after ISDN was infused (P < 0.001); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (18.42± 5.17)% at baseline, (14.18±3.61)% after ISDN was infused (P< 0.001); the sum of defect blood ST segments was 64 at baseline, 41 after ISDN was infused. Conclusions The unfolded surface mapping of 99mTc- MIBI myocardial perfusion image can be used as a method of quantitatively evaluating the anti-ischemic effect of drugs and ISDN iv drip can improve the blood flow in myocardium (myocardium perfusion).展开更多
AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitropruside (SNP) in internal anal sphincter (IAS) smooth muscle. METHODS...AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitropruside (SNP) in internal anal sphincter (IAS) smooth muscle. METHODS: Relaxation responses of ISDN, and electrical fi eld stimulation (EFS) were obtained before and after tolerance induction by ISDN incubation. RESULTS: ISDN (10-7-10-4 mol/L) and SNP (10-8-10-4 mol/L) caused a concentration-dependent relaxation on the basal tonus of the isolated rabbit IAS strips. After a period of 2 h incubation of the 6 x 10-4 mol/L ISDN the relaxation effects of ISDN and SNP did not change compared to control strips. EFS evoked frequency-dependent relaxation in internal anal sphincter smooth muscle and Emax obtained from control strips were not changed in ISDN tolerance-inducing condition. In this study nitrate tolerance was not observed in rabbit IAS smooth muscle. CONCLUSION: This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance.展开更多
基金‘863'High Technology R&D Project of Ministry of Science and Technology of China(Grant No.2004AA2Z3073).
文摘The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.
文摘Objectives To evaluate the anti- ischemic effect of ISDN on the patients with coronary heart disease . The change in the size of the defect area as percentage of the entire myocardium as determined by the unfolded surface mapping between the baseline and after ISDN infusion reflects the anti-ischemic effect of ISDN. Methods and Results 99m Tc-MIBI myocardial perfusion SPECT images were acquired, and reconstruction of the bull's eye map and unfolded surface mapping were performed according to the dates of tomography images. In the group (99mTc-MIBI was injected at 30 minutes after the start of ISDN iv drip) : at the 65% threshold value, the percentage of the defect area size in the whole ventricle was 33.01 ± 5.35% at baseline, (28.9 ±5.23)% after ISDN was infused (P < 0.05); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (22.06±5.58)% at baseline, (19.60±4.07)% after ISDN was infused (P < 0.05); the sum of defect blood ST segments is 60 at baseline, 51 after ISDN was infused. In the group (99mTc-MIBI was injected at 60 minutes after the start of ISDN iv drip): at the 65% threshold value, the percentage of the defect area size in the whole ventricle was (29.20±5.08)% at baseline, (20.81±4.16)% after ISDN was infused (P < 0.001); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (21.2 ± 5.49)% at baseline, (17.52±5.59)% after ISDN was infused (P < 0.001); the sum of defect blood ST segments is 58 at baseline, 47 after ISDN was infused. In the group (99mTc-MIBI was injected at 150 minutes after the start of ISDN iv drip) : at the 65% threshold value, the percentage of the defect area size in the whole ventricle was (32.87 ±6.46)% at baseline, (20.81±4.16)% after ISDN was infused (P < 0.001); at the 55% threshold value, the percentage of the defect area size in the whole ventricle was (18.42± 5.17)% at baseline, (14.18±3.61)% after ISDN was infused (P< 0.001); the sum of defect blood ST segments was 64 at baseline, 41 after ISDN was infused. Conclusions The unfolded surface mapping of 99mTc- MIBI myocardial perfusion image can be used as a method of quantitatively evaluating the anti-ischemic effect of drugs and ISDN iv drip can improve the blood flow in myocardium (myocardium perfusion).
文摘AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitropruside (SNP) in internal anal sphincter (IAS) smooth muscle. METHODS: Relaxation responses of ISDN, and electrical fi eld stimulation (EFS) were obtained before and after tolerance induction by ISDN incubation. RESULTS: ISDN (10-7-10-4 mol/L) and SNP (10-8-10-4 mol/L) caused a concentration-dependent relaxation on the basal tonus of the isolated rabbit IAS strips. After a period of 2 h incubation of the 6 x 10-4 mol/L ISDN the relaxation effects of ISDN and SNP did not change compared to control strips. EFS evoked frequency-dependent relaxation in internal anal sphincter smooth muscle and Emax obtained from control strips were not changed in ISDN tolerance-inducing condition. In this study nitrate tolerance was not observed in rabbit IAS smooth muscle. CONCLUSION: This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance.
