Ischemia-induced angiogenic response is reduced in spontaneously hypertensive rats (SHR). To study whether exogenous basic fibroblast growth factor (bFGF) infusion is effective in expanding collateral circulation in frankly hypertensive SHR, femoral arteries of male SHR (weighing ∼250 g) were kept intact (nonoccluded control; n = 9) or occluded for4h( n = 12) or for 16 days with vehicle ( n = 14) or bFGF [0.5 ( n = 17), 5.0 ( n = 13), and 50.0 ( n = 14) μg · kg–1 · day–1 for 14 days] intraarterially. Maximal collateral-dependent blood flows (BF) to the hindlimbs were determined with 85Sr- and 141Ce-labeled microspheres during running at 20 and 25 m/min (15% grade). Preexercise heart rates (∼530 beats/min) and blood pressures (BP; ∼200 mmHg) were similar across groups except in the high-dose bFGF group, where BP was reduced by ∼12% ( P < 0.05). Femoral artery occlusion for 4 h resulted in ∼95% reduction of BF in calf muscles [199 ± 18.7 (nonoccluded group) to 10 ± 1.0 ml · min–1 · 100 g–1; P < 0.001]. BF to calf muscles of the vehicle and low-dose bFGF (0.5 μg · kg–1 · day–1) groups increased to 36 ± 3.2 and 45 ± 2.0 ml · min–1 · 100 g–1, respectively ( P < 0.001). bFGF infusion at 5.0 and 50.0 μg · kg–1 · day–1 further increased ( P < 0.001) BF to calf muscles (62 ± 4.6 and 62 ± 2.2 ml · min–1 · 100 g–1, respectively). Our results show that bFGF can effectively increase BF in hypertensive rats. The reduced hypertension with high-dose bFGF suggests that a critical signal in arteriogenesis (nitric oxide bioavailability) may be restored. These findings suggest that the dulled endothelial nitric oxide synthase of SHR does not preempt collateral vessel remodeling.
Constitutively synthesized nitric oxide is a physiological negative regulator of mammalian angiogenesis mediated by basic fibroblast growth factor
