Effects of FK506 in rat and human resistance arteries

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Presentation transcript:

Effects of FK506 in rat and human resistance arteries Jose J.G. De Lima, Hong Xue, Leon Coburn, Takeshi F. Andoh, David A. Mccarron, William M. Bennett, Jean-Baptiste Roullet Kidney International Volume 55, Issue 4, Pages 1518-1527 (April 1999) DOI: 10.1046/j.1523-1755.1999.00366.x Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 1 In vitro effect of FK506 on human arteries (N = 7). Isolated arteries were exposed for 24hours with 1000ng/ml FK506 (◊) or vehicle (•), contracted with norepinephrine (NE), and challenged with cumulative dose of acetylcholine (A) or sodium nitroprusside (B), as described in the Methods section. Asterisks indicate a significant (P < 0.05) difference between the two groups. SNp-ED50 values in controls was 158 ± 97nm and in FK506 was 264 ± 123nm (P < 0.01). Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 2 Effect of FK506 (short-term treatment) on NE-induced contraction in isolated rat arteries (ex vivo studies). Arteries isolated from FK506-treated (◊) and control (•) animals (N = 11 per group) were challenged with a cumulative dose of NE. Asterisks indicate a significant (P < 0.05) difference between the two groups. Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 3 Effect of FK506 (short-term treatment) on Ach-induced relaxation in isolated rat arteries (ex vivo studies). Arteries isolated from FK506-treated (◊) and control (•) animals (N = 11 per group) were contracted with NE and challenged with cumulative dose of Ach. Relaxation to Ach was determined in basal conditions (A) or after incubation with l-arginine (B) (300 μm for 20min). Asterisks indicate a significant (P < 0.05) difference between the two experimental groups. Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 4 Effect of FK506 (short-term treatment) on SNp-induced relaxation in isolated rat arteries (ex vivo studies). Arteries isolated from FK506-treated (◊) and control (•) animals (N = 11 per group) were contracted with NE and challenged with cumulative dose of SNp. Asterisks indicate a significant (P < 0.05) difference between the two experimental groups. Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 5 Effect of FK506 (short-term treatment) on blood pressure and heart rate responsiveness to NE in the rat (in vivo studies). FK506-treated (◊) and control (•) animals (N = 10/group) were instrumented as described in the Methods section. Mean arterial pressure (MAP; A) and heart rate (B) responsiveness (peak response - baseline) was determined after bolus injections of NE (Methods section). Asterisks indicate a significant (P < 0.05) difference between the two groups. Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 6 Effects of FK506 (short-term treatment) on blood pressure and heart rate responsiveness to Ach in the rat (in vivo studies). FK506-treated (◊) and control (•) animals (N = 10/group) were instrumented as described in the Methods section. Blood pressure [mean arterial pressure (MAP), A] and heart rate (B) responsiveness (peak response - baseline) were determined after a five-minute infusion of Ach (Methods section). Asterisks indicate a significant (P < 0.05) difference between the two groups. Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 7 Effect of FK506 (long-term treatment) on Ach-induced relaxation in isolated rat arteries (ex vivo studies). (A) Arteries isolated from FK506-treated (◊) and control (•) animals (N = 9 per group) were contracted with NE and challenged with a cumulative dose of Ach in basal conditions (asterisks indicate a significant difference between the two groups). Relaxation to Ach was also conducted after incubation with indomethacin or with a mixture of indomethacin and methylene blue. The maximum responses to Ach (expressed as percentage of precontraction with NE) in all three conditions are shown in (B). Symbols are: (▪) control; (□) FK506-treated animals. Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions

Figure 8 Effect of FK506 (long-term treatment) on SNp-induced relaxation in isolated rat arteries (ex vivo studies). Arteries isolated from FK506-treated (◊) and control (•) animals (N = 9 per group) were contracted with NE and challenged with cumulative dose of SNp. Asterisks indicate a significant (P < 0.05) difference between the two experimental groups. Kidney International 1999 55, 1518-1527DOI: (10.1046/j.1523-1755.1999.00366.x) Copyright © 1999 International Society of Nephrology Terms and Conditions