The aim of the present study was to assess the effects of angiotensin coverting enzyme inhibitor ... more The aim of the present study was to assess the effects of angiotensin coverting enzyme inhibitor (ACE-I) perindopril and angiotensin receptor blocker (ARB) candesartan on the survival of Dahl salt-sensitive (DS) hypertensive rats. In addition, we also studied the effects of ACE-I and ARB on LV contractile dysfunction and LV fibrosis for exploring to the mechanism contributing to the improvement of the survival. Methods: At the age of 6 weeks, the DS rats were divided into the following four groups: DS rats fed a low-salt diet (group LS); DS rats fed a high-salt diet (group HS); DS rats fed a high-salt diet and treated with perindopril [1mg/kg/day] (group HS-P), and DS rats fed a high-salt diet and treated with candesartan [1mg/kg/day] (group HS-C). At the age of 16 weeks, studies of systemic and cardiac hemodynamics, LV remodeling and LV fibrosis were then evaluated. Results: Compared with the HS group, systolic blood pressure in both the HS-P group and the HS-C group did not significantly decrease and although the transition to systolic heart failure was inhibited, LV hypertrophy did develop in both groups. LV contractile function in both groups improved to almost the same degree as that in the LS group. The effect of perindopril was a fraction greater than that of candesartan (%FS: 49.9 Ϯ 6.8%, 45.7 Ϯ 5.4%, respectively) as opposed to the HS group figures of 33.9 Ϯ 7.0%. In contrast, the 100-day survival rate in the HS-C group significantly improved compared to that in the HS-P group (100% to 40%, respectively). Histological examinations using Azan-Mallory stain demonstrated that that candesartan had more success than perindopril in decreasing LV fibrosis. Conclusion: The study showed that candesartan significantly improved survival rate compared to perindopril in DS hypertensive rats. Candesartan was far more successful than perindopril in decreasing LV fibrosis, which is probably a key factor in improving the survival rate for hypertensive heart failure.
The vascular effects induced by chronic testosterone (TS) deficiency in men is not totally clear.... more The vascular effects induced by chronic testosterone (TS) deficiency in men is not totally clear. Thus, we assessed vascular reactivity in the forearm microcirculation of congenital hypogonadal patients (HP), at baseline and after 6-month TS replacement therapy (TS enanthate, 100-250 mg i.m. every 3 weeks). In 8 HP (28.6Ϯ2.8 years, with hypogonadotropic, nϭ6, or hypergonadotropic, nϭ2, hypogonadism; blood pressure, BP, 123Ϯ6/78Ϯ4 mmHg) and 9 male matched control subjects (CS, 29.0Ϯ1.7 years; BP 122Ϯ2/78Ϯ1 mmHg) we studied forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (ACH, 0.15-15 mg/100 ml/min), an endotheliumdependent agonist, or sodium nitroprusside (SNP, 1-4 mg/100 ml/min), utilized as direct smooth muscle cell vasodilator. ACH was repeated during intrabrachial L-NMMA infusion (100 g/100 ml/min), a nitric oxide (NO) inhibitor. At baseline, in HP the percent maximal vasodilation (VD) to ACH (387Ϯ79%) was significantly (pϽ0.01) reduced as compared to CS (753Ϯ106%). As expected, in CS the VD to ACH was significantly blunted by L-NMMA (268Ϯ47%, inhibition: 64.4%). In contrast, in HP the inhibitory effect of L-NMMA on maximal response to ACH was reduced (297Ϯ35%, inhibition: 23.3% pϽ0.001 vs CS). At baseline, the VD to SNP also resulted to be lower in HP (347Ϯ54%) compared with CS (574Ϯ59%, pϽ0.05). TS therapy did not modify BP levels (114Ϯ5/78Ϯ5 mmHg). In contrast, hormone replacement therapy increased (pϽ0.05) plasma free TS (41.3Ϯ12.8 vs 9.7Ϯ3.1 pmol/L) and total TS (11.3Ϯ3.1 vs 2.8Ϯ1.1 nmol/L), without modifying 17- estradiol and estrone values. TS therapy reduced HDL cholesterol (1.11Ϯ0.06 vs 1.3Ϯ0.07 mmol/L, pϽ0.01) and total cholesterol (4.1Ϯ0.3 vs 4.7Ϯ0.4 mmol/L), while not modifying plasma triglycerides and LDL cholesterol. TS therapy further reduced the vascular response to ACH (187Ϯ29%, pϽ0.01 vs baseline) and abrogated the inhibition by L-NMMA on ACH (180Ϯ37%; inhibition: 3.2%) compared with pre-intervention results. TS totally unaffected the VD to SNP (355Ϯ47%). Congenital HP are characterized by a reduced vascular reactivity, including an endothelial dysfunction due to a reduced NO availability. Chronic TS administration selectively impairs NO availability in these patients.
The aim of the present study was to assess the effects of angiotensin coverting enzyme inhibitor ... more The aim of the present study was to assess the effects of angiotensin coverting enzyme inhibitor (ACE-I) perindopril and angiotensin receptor blocker (ARB) candesartan on the survival of Dahl salt-sensitive (DS) hypertensive rats. In addition, we also studied the effects of ACE-I and ARB on LV contractile dysfunction and LV fibrosis for exploring to the mechanism contributing to the improvement of the survival. Methods: At the age of 6 weeks, the DS rats were divided into the following four groups: DS rats fed a low-salt diet (group LS); DS rats fed a high-salt diet (group HS); DS rats fed a high-salt diet and treated with perindopril [1mg/kg/day] (group HS-P), and DS rats fed a high-salt diet and treated with candesartan [1mg/kg/day] (group HS-C). At the age of 16 weeks, studies of systemic and cardiac hemodynamics, LV remodeling and LV fibrosis were then evaluated. Results: Compared with the HS group, systolic blood pressure in both the HS-P group and the HS-C group did not significantly decrease and although the transition to systolic heart failure was inhibited, LV hypertrophy did develop in both groups. LV contractile function in both groups improved to almost the same degree as that in the LS group. The effect of perindopril was a fraction greater than that of candesartan (%FS: 49.9 Ϯ 6.8%, 45.7 Ϯ 5.4%, respectively) as opposed to the HS group figures of 33.9 Ϯ 7.0%. In contrast, the 100-day survival rate in the HS-C group significantly improved compared to that in the HS-P group (100% to 40%, respectively). Histological examinations using Azan-Mallory stain demonstrated that that candesartan had more success than perindopril in decreasing LV fibrosis. Conclusion: The study showed that candesartan significantly improved survival rate compared to perindopril in DS hypertensive rats. Candesartan was far more successful than perindopril in decreasing LV fibrosis, which is probably a key factor in improving the survival rate for hypertensive heart failure.
The vascular effects induced by chronic testosterone (TS) deficiency in men is not totally clear.... more The vascular effects induced by chronic testosterone (TS) deficiency in men is not totally clear. Thus, we assessed vascular reactivity in the forearm microcirculation of congenital hypogonadal patients (HP), at baseline and after 6-month TS replacement therapy (TS enanthate, 100-250 mg i.m. every 3 weeks). In 8 HP (28.6Ϯ2.8 years, with hypogonadotropic, nϭ6, or hypergonadotropic, nϭ2, hypogonadism; blood pressure, BP, 123Ϯ6/78Ϯ4 mmHg) and 9 male matched control subjects (CS, 29.0Ϯ1.7 years; BP 122Ϯ2/78Ϯ1 mmHg) we studied forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (ACH, 0.15-15 mg/100 ml/min), an endotheliumdependent agonist, or sodium nitroprusside (SNP, 1-4 mg/100 ml/min), utilized as direct smooth muscle cell vasodilator. ACH was repeated during intrabrachial L-NMMA infusion (100 g/100 ml/min), a nitric oxide (NO) inhibitor. At baseline, in HP the percent maximal vasodilation (VD) to ACH (387Ϯ79%) was significantly (pϽ0.01) reduced as compared to CS (753Ϯ106%). As expected, in CS the VD to ACH was significantly blunted by L-NMMA (268Ϯ47%, inhibition: 64.4%). In contrast, in HP the inhibitory effect of L-NMMA on maximal response to ACH was reduced (297Ϯ35%, inhibition: 23.3% pϽ0.001 vs CS). At baseline, the VD to SNP also resulted to be lower in HP (347Ϯ54%) compared with CS (574Ϯ59%, pϽ0.05). TS therapy did not modify BP levels (114Ϯ5/78Ϯ5 mmHg). In contrast, hormone replacement therapy increased (pϽ0.05) plasma free TS (41.3Ϯ12.8 vs 9.7Ϯ3.1 pmol/L) and total TS (11.3Ϯ3.1 vs 2.8Ϯ1.1 nmol/L), without modifying 17- estradiol and estrone values. TS therapy reduced HDL cholesterol (1.11Ϯ0.06 vs 1.3Ϯ0.07 mmol/L, pϽ0.01) and total cholesterol (4.1Ϯ0.3 vs 4.7Ϯ0.4 mmol/L), while not modifying plasma triglycerides and LDL cholesterol. TS therapy further reduced the vascular response to ACH (187Ϯ29%, pϽ0.01 vs baseline) and abrogated the inhibition by L-NMMA on ACH (180Ϯ37%; inhibition: 3.2%) compared with pre-intervention results. TS totally unaffected the VD to SNP (355Ϯ47%). Congenital HP are characterized by a reduced vascular reactivity, including an endothelial dysfunction due to a reduced NO availability. Chronic TS administration selectively impairs NO availability in these patients.
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Papers by Jorge Jimenez