Figure 4.
Effect of NOS and COX inhibition on the concentration-dependent reversal of pressure-induced constriction (at 60 mmHg) by BK (0.01–100 nmol/L) in C and Beta MCA. A: In C MCA, inhibition of NOS with L-NAME (100 μmol/L) significantly shifted the BK dose-response curve to the right without affecting maximal dilation to BK. (N=4; C: ■; C+L-NAME: □; pD2: C = −9.50±0.09 vs. C+L-NAME = −8.33±0.32, p=0.012; Top: C = 100.40±3.19 vs. C+L-NAME = 98.40±15.90, p=0.9005; Bottom: C = +17.83±4.60 vs. C+L-NAME = −10.23±9.53, p=0.499; concentration response curves were found to be significantly different using a three-parameter curve fit: p=0.021). B: In Beta MCA, inhibition of NOS with L-NAME (100 μmol/L) significantly shifted the BK dose-response curve to the right and reduced maximal dilation to BK. (N=4; Beta: ●; Beta+L-NAME: ○; pD2: Beta = −8.84±0.05 vs. Beta+L-NAME = −8.59±0.088, p=0.049; Top: Beta= 88.16±1.74 vs. Beta+L-NAME = 26.70±1.41; p<0.0001, Bottom: Beta = −6.70±1.582 vs. Beta+L-NAME = 12.53±1.06, p=0.014; concentration response curves were found to be significantly different using a three-parameter parameter curve fit: p<0.0001). C: In C MCA, inhibition of COX with Indo (10 μmol/L) had no effect on the BK dose-response curve. (N=4; C: ◆; C+Indo: ◇; pD2: C = −9.56±0.16 vs. C+Indo = −9.06±0.36, p=0.2577; Top: C = 76.66±3.22 vs. C+Indo = 69.99±9.86, p=0.5056; Bottom: C = 3.74±4.96 vs. C+Indo = −9.60±10.29, p=0.3152; concentration response curves were not different as assessed using a three-parameter curve fit: p=0.1022). D: In Beta MCA, inhibition of COX with Indo (10 μmol/L) shifted the BK dose-response curve significantly to the right without affecting maximal dilation to BK. (N=5; Beta: ▲; Beta+Indo: △; pD2: Beta = −9.26±0.05 vs. Beta+Indo = −8.39±0.19, p=0.005; Top: Beta = 85.31±1.80 vs. Beta+Indo = 67.51±5.78, p=0.026; Bottom: Beta = −7.42±2.13 vs. Beta+Indo = −0.67±3.67, p=0.1631; concentration response curves were found to be significantly different using a three-parameter parameter curve fit: p=0.0032).