The Experts below are selected from a list of 6 Experts worldwide ranked by ideXlab platform

Toshio Miyata - One of the best experts on this subject based on the ideXlab platform.

  • a Sartan Derivative with a very low angiotensin ii receptor affinity ameliorates ischemic cerebral damage
    Journal of Cerebral Blood Flow and Metabolism, 2009
    Co-Authors: Shunya Takizawa, Takashi Dan, Tsuyoshi Uesugi, Eiichiro Nagata, Shigeharu Takagi, Charles Van Ypersele De Strihou, Toshio Miyata
    Abstract:

    Angiotensin II receptor blockers (ARBs) have a potent ability to inhibit oxidative stress and advanced glycation, in addition to their protective effects originated from blood pressure lowering and angiotensin II type 1 receptor (AT(1))-blockade. To obtain a pharmacological tool to dissect the mechanisms of ARBs' protective benefits in experimental stroke, we synthesized a novel ARB-Derivative, R-147176, which is 6,700 times less potent than olmeSartan in AT(1)-binding inhibition and therefore has a minimal antihypertensive effect, but retains marked inhibitory effects on oxidative stress and advanced glycation. We evaluated the effect of R-147176 (10-30 mg/kg per day), administered orally or intravenously, on brain infarct volume in transient thread occlusion and photothrombotic models in rats. The antioxidative and antiinflammatory properties were also investigated. R-147176 significantly reduced infarct volume, without influence on blood pressure, in both models. R-147176 significantly reduced the numbers of ED-1-positive cells and of TUNEL-positive cells, and protein carbonyl formation in the damaged brain. This ARB Derivative, despite its significantly lower AT1 affinity and virtually no antihypertensive effect, ameliorated ischemic cerebral damage through antioxidative and antiinflammatory properties. These findings suggest potential usefulness of R-147176 as a pharmacological tool to investigate the ARBs' protective effect in experimental stroke and open new therapeutic avenues. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1665-1672; doi:10.1038/jcbfm.2009.82; published online 17 June 2009

  • a novel Sartan Derivative with very low angiotensin ii type 1 receptor affinity protects the kidney in type 2 diabetic rats
    Arteriosclerosis Thrombosis and Vascular Biology, 2008
    Co-Authors: Yuko Izuhara, Takashi Dan, Charles Van Ypersele De Strihou, Toshio Sada, Hiroaki Yanagisawa, Hiroyuki Koike, Shuichi Ohtomo, Sadayoshi Ito, Masaomi Nangaku, Toshio Miyata
    Abstract:

    Background-Antihypertensive angiotensin II receptor blockers (ARBs) protect the kidney, at least in part, independently of blood pressure lowering. Still, the extent to which blood pressure lowering is related to renoprotection remains unclear. METHODS AND RESULTS: 139 newly synthesized ARB-Derivatives were assayed for inhibition of advanced glycation (AGEs). The 9 most powerful compounds were then tested for transition metal chelation, angiotensin II type 1 receptor (AT1R) affinity, and pharmacokinetic parameters. R-147176 was eventually selected as it strongly inhibits advanced glycation but is 6700 times less effective than olmeSartan in AT1R binding. It is orally bioavailable and toxicologically safe. Despite a minimal blood pressure lowering effect, it provides significant renoprotection in 3 experimental rat models with renal injury, ie, obese, hypertensive, type 2 diabetic rats (SHR/NDmcr-cp), normotensive type 2 diabetic rats (Zucker diabetic fatty), and remnant kidney rats. CONCLUSIONS: R-147176 retains renal protective properties despite a minimal blood pressure-lowering effect. Clearly, the renal benefits of ARBs do not necessarily depend on blood pressure lowering and AT1R affinity, but rather on the inhibition of AGEs and oxidative stress inherent to their chemical structure. R-147176 opens new avenues in the treatment of cardiovascular and kidney diseases.

Takashi Dan - One of the best experts on this subject based on the ideXlab platform.

  • a Sartan Derivative with a very low angiotensin ii receptor affinity ameliorates ischemic cerebral damage
    Journal of Cerebral Blood Flow and Metabolism, 2009
    Co-Authors: Shunya Takizawa, Takashi Dan, Tsuyoshi Uesugi, Eiichiro Nagata, Shigeharu Takagi, Charles Van Ypersele De Strihou, Toshio Miyata
    Abstract:

    Angiotensin II receptor blockers (ARBs) have a potent ability to inhibit oxidative stress and advanced glycation, in addition to their protective effects originated from blood pressure lowering and angiotensin II type 1 receptor (AT(1))-blockade. To obtain a pharmacological tool to dissect the mechanisms of ARBs' protective benefits in experimental stroke, we synthesized a novel ARB-Derivative, R-147176, which is 6,700 times less potent than olmeSartan in AT(1)-binding inhibition and therefore has a minimal antihypertensive effect, but retains marked inhibitory effects on oxidative stress and advanced glycation. We evaluated the effect of R-147176 (10-30 mg/kg per day), administered orally or intravenously, on brain infarct volume in transient thread occlusion and photothrombotic models in rats. The antioxidative and antiinflammatory properties were also investigated. R-147176 significantly reduced infarct volume, without influence on blood pressure, in both models. R-147176 significantly reduced the numbers of ED-1-positive cells and of TUNEL-positive cells, and protein carbonyl formation in the damaged brain. This ARB Derivative, despite its significantly lower AT1 affinity and virtually no antihypertensive effect, ameliorated ischemic cerebral damage through antioxidative and antiinflammatory properties. These findings suggest potential usefulness of R-147176 as a pharmacological tool to investigate the ARBs' protective effect in experimental stroke and open new therapeutic avenues. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1665-1672; doi:10.1038/jcbfm.2009.82; published online 17 June 2009

  • a novel Sartan Derivative with very low angiotensin ii type 1 receptor affinity protects the kidney in type 2 diabetic rats
    Arteriosclerosis Thrombosis and Vascular Biology, 2008
    Co-Authors: Yuko Izuhara, Takashi Dan, Charles Van Ypersele De Strihou, Toshio Sada, Hiroaki Yanagisawa, Hiroyuki Koike, Shuichi Ohtomo, Sadayoshi Ito, Masaomi Nangaku, Toshio Miyata
    Abstract:

    Background-Antihypertensive angiotensin II receptor blockers (ARBs) protect the kidney, at least in part, independently of blood pressure lowering. Still, the extent to which blood pressure lowering is related to renoprotection remains unclear. METHODS AND RESULTS: 139 newly synthesized ARB-Derivatives were assayed for inhibition of advanced glycation (AGEs). The 9 most powerful compounds were then tested for transition metal chelation, angiotensin II type 1 receptor (AT1R) affinity, and pharmacokinetic parameters. R-147176 was eventually selected as it strongly inhibits advanced glycation but is 6700 times less effective than olmeSartan in AT1R binding. It is orally bioavailable and toxicologically safe. Despite a minimal blood pressure lowering effect, it provides significant renoprotection in 3 experimental rat models with renal injury, ie, obese, hypertensive, type 2 diabetic rats (SHR/NDmcr-cp), normotensive type 2 diabetic rats (Zucker diabetic fatty), and remnant kidney rats. CONCLUSIONS: R-147176 retains renal protective properties despite a minimal blood pressure-lowering effect. Clearly, the renal benefits of ARBs do not necessarily depend on blood pressure lowering and AT1R affinity, but rather on the inhibition of AGEs and oxidative stress inherent to their chemical structure. R-147176 opens new avenues in the treatment of cardiovascular and kidney diseases.

Charles Van Ypersele De Strihou - One of the best experts on this subject based on the ideXlab platform.

  • a Sartan Derivative with a very low angiotensin ii receptor affinity ameliorates ischemic cerebral damage
    Journal of Cerebral Blood Flow and Metabolism, 2009
    Co-Authors: Shunya Takizawa, Takashi Dan, Tsuyoshi Uesugi, Eiichiro Nagata, Shigeharu Takagi, Charles Van Ypersele De Strihou, Toshio Miyata
    Abstract:

    Angiotensin II receptor blockers (ARBs) have a potent ability to inhibit oxidative stress and advanced glycation, in addition to their protective effects originated from blood pressure lowering and angiotensin II type 1 receptor (AT(1))-blockade. To obtain a pharmacological tool to dissect the mechanisms of ARBs' protective benefits in experimental stroke, we synthesized a novel ARB-Derivative, R-147176, which is 6,700 times less potent than olmeSartan in AT(1)-binding inhibition and therefore has a minimal antihypertensive effect, but retains marked inhibitory effects on oxidative stress and advanced glycation. We evaluated the effect of R-147176 (10-30 mg/kg per day), administered orally or intravenously, on brain infarct volume in transient thread occlusion and photothrombotic models in rats. The antioxidative and antiinflammatory properties were also investigated. R-147176 significantly reduced infarct volume, without influence on blood pressure, in both models. R-147176 significantly reduced the numbers of ED-1-positive cells and of TUNEL-positive cells, and protein carbonyl formation in the damaged brain. This ARB Derivative, despite its significantly lower AT1 affinity and virtually no antihypertensive effect, ameliorated ischemic cerebral damage through antioxidative and antiinflammatory properties. These findings suggest potential usefulness of R-147176 as a pharmacological tool to investigate the ARBs' protective effect in experimental stroke and open new therapeutic avenues. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1665-1672; doi:10.1038/jcbfm.2009.82; published online 17 June 2009

  • a novel Sartan Derivative with very low angiotensin ii type 1 receptor affinity protects the kidney in type 2 diabetic rats
    Arteriosclerosis Thrombosis and Vascular Biology, 2008
    Co-Authors: Yuko Izuhara, Takashi Dan, Charles Van Ypersele De Strihou, Toshio Sada, Hiroaki Yanagisawa, Hiroyuki Koike, Shuichi Ohtomo, Sadayoshi Ito, Masaomi Nangaku, Toshio Miyata
    Abstract:

    Background-Antihypertensive angiotensin II receptor blockers (ARBs) protect the kidney, at least in part, independently of blood pressure lowering. Still, the extent to which blood pressure lowering is related to renoprotection remains unclear. METHODS AND RESULTS: 139 newly synthesized ARB-Derivatives were assayed for inhibition of advanced glycation (AGEs). The 9 most powerful compounds were then tested for transition metal chelation, angiotensin II type 1 receptor (AT1R) affinity, and pharmacokinetic parameters. R-147176 was eventually selected as it strongly inhibits advanced glycation but is 6700 times less effective than olmeSartan in AT1R binding. It is orally bioavailable and toxicologically safe. Despite a minimal blood pressure lowering effect, it provides significant renoprotection in 3 experimental rat models with renal injury, ie, obese, hypertensive, type 2 diabetic rats (SHR/NDmcr-cp), normotensive type 2 diabetic rats (Zucker diabetic fatty), and remnant kidney rats. CONCLUSIONS: R-147176 retains renal protective properties despite a minimal blood pressure-lowering effect. Clearly, the renal benefits of ARBs do not necessarily depend on blood pressure lowering and AT1R affinity, but rather on the inhibition of AGEs and oxidative stress inherent to their chemical structure. R-147176 opens new avenues in the treatment of cardiovascular and kidney diseases.

Shunya Takizawa - One of the best experts on this subject based on the ideXlab platform.

  • a Sartan Derivative with a very low angiotensin ii receptor affinity ameliorates ischemic cerebral damage
    Journal of Cerebral Blood Flow and Metabolism, 2009
    Co-Authors: Shunya Takizawa, Takashi Dan, Tsuyoshi Uesugi, Eiichiro Nagata, Shigeharu Takagi, Charles Van Ypersele De Strihou, Toshio Miyata
    Abstract:

    Angiotensin II receptor blockers (ARBs) have a potent ability to inhibit oxidative stress and advanced glycation, in addition to their protective effects originated from blood pressure lowering and angiotensin II type 1 receptor (AT(1))-blockade. To obtain a pharmacological tool to dissect the mechanisms of ARBs' protective benefits in experimental stroke, we synthesized a novel ARB-Derivative, R-147176, which is 6,700 times less potent than olmeSartan in AT(1)-binding inhibition and therefore has a minimal antihypertensive effect, but retains marked inhibitory effects on oxidative stress and advanced glycation. We evaluated the effect of R-147176 (10-30 mg/kg per day), administered orally or intravenously, on brain infarct volume in transient thread occlusion and photothrombotic models in rats. The antioxidative and antiinflammatory properties were also investigated. R-147176 significantly reduced infarct volume, without influence on blood pressure, in both models. R-147176 significantly reduced the numbers of ED-1-positive cells and of TUNEL-positive cells, and protein carbonyl formation in the damaged brain. This ARB Derivative, despite its significantly lower AT1 affinity and virtually no antihypertensive effect, ameliorated ischemic cerebral damage through antioxidative and antiinflammatory properties. These findings suggest potential usefulness of R-147176 as a pharmacological tool to investigate the ARBs' protective effect in experimental stroke and open new therapeutic avenues. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1665-1672; doi:10.1038/jcbfm.2009.82; published online 17 June 2009

Tsuyoshi Uesugi - One of the best experts on this subject based on the ideXlab platform.

  • a Sartan Derivative with a very low angiotensin ii receptor affinity ameliorates ischemic cerebral damage
    Journal of Cerebral Blood Flow and Metabolism, 2009
    Co-Authors: Shunya Takizawa, Takashi Dan, Tsuyoshi Uesugi, Eiichiro Nagata, Shigeharu Takagi, Charles Van Ypersele De Strihou, Toshio Miyata
    Abstract:

    Angiotensin II receptor blockers (ARBs) have a potent ability to inhibit oxidative stress and advanced glycation, in addition to their protective effects originated from blood pressure lowering and angiotensin II type 1 receptor (AT(1))-blockade. To obtain a pharmacological tool to dissect the mechanisms of ARBs' protective benefits in experimental stroke, we synthesized a novel ARB-Derivative, R-147176, which is 6,700 times less potent than olmeSartan in AT(1)-binding inhibition and therefore has a minimal antihypertensive effect, but retains marked inhibitory effects on oxidative stress and advanced glycation. We evaluated the effect of R-147176 (10-30 mg/kg per day), administered orally or intravenously, on brain infarct volume in transient thread occlusion and photothrombotic models in rats. The antioxidative and antiinflammatory properties were also investigated. R-147176 significantly reduced infarct volume, without influence on blood pressure, in both models. R-147176 significantly reduced the numbers of ED-1-positive cells and of TUNEL-positive cells, and protein carbonyl formation in the damaged brain. This ARB Derivative, despite its significantly lower AT1 affinity and virtually no antihypertensive effect, ameliorated ischemic cerebral damage through antioxidative and antiinflammatory properties. These findings suggest potential usefulness of R-147176 as a pharmacological tool to investigate the ARBs' protective effect in experimental stroke and open new therapeutic avenues. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1665-1672; doi:10.1038/jcbfm.2009.82; published online 17 June 2009