PURPOSE: Olprinone, one of the most frequently used phosphodiesterase-3 inhibitors, exerts its positive inotropic and vasodilation effects by inhibiting the degradation of intracellular cyclic adenosine monophosphate (cAMP). The vasodilation response to olprinone is not uniform among the different vascular beds. This study was designed to compare the vasorelaxation response to olprinone between renal and common carotid arteries, and investigate its underlying mechanisms. METHODS: Isometric force measurement, enzyme immunoassay, and western blotting techniques were used to investigate the vasorelaxation action of olprinone in isolated rabbit renal and common carotid arteries. RESULTS: Olprinone inhibited the contractile response to phenylephrine (PE) both in the renal and carotid arteries in a concentration-dependent manner with IC50 values of 40 +/- 10 and 103 +/- 43 nM, respectively. The IC50 value was lower (P = 0.004) and the maximal inhibition was greater (P = 0.002) in the renal artery compared with the carotid artery. A cell-permeable cAMP analogue, 8-bromo-cAMP, also inhibited the contractile response to PE in the renal and carotid arteries with IC50 values of 581 +/- 150 and 740 +/- 179 microM, respectively; however no differences were observed both in the IC50 value and the maximal inhibition between two arteries. Olprinone (0.1 microM) increased the intracellular cAMP level in the renal arterial smooth muscle cells (ASMCs) but not in the carotid ASMCs. The expression of PDE3A was greater (P = 0.008) in the carotid ASMCs than the renal ASMCs. CONCLUSION: The enhanced vasodilator action of olprinone in the renal artery is presumably because of its ability to stimulate the cAMP production, which might be attributable to the heterogeneous expression of PDE3A.
PURPOSE:Olprinone, one of the most frequently used phosphodiesterase-3 inhibitors, exerts its positive inotropic and vasodilation effects by inhibiting the degradation of intracellular cyclic adenosine monophosphate (cAMP). The vasodilation response to olprinone is not uniform among the different vascular beds. This study was designed to compare the vasorelaxation response to olprinone between renal and common carotid arteries, and investigate its underlying mechanisms. METHODS: Isometric force measurement, enzyme immunoassay, and western blotting techniques were used to investigate the vasorelaxation action of olprinone in isolated rabbit renal and common carotid arteries. RESULTS:Olprinone inhibited the contractile response to phenylephrine (PE) both in the renal and carotid arteries in a concentration-dependent manner with IC50 values of 40 +/- 10 and 103 +/- 43 nM, respectively. The IC50 value was lower (P = 0.004) and the maximal inhibition was greater (P = 0.002) in the renal artery compared with the carotid artery. A cell-permeable cAMP analogue, 8-bromo-cAMP, also inhibited the contractile response to PE in the renal and carotid arteries with IC50 values of 581 +/- 150 and 740 +/- 179 microM, respectively; however no differences were observed both in the IC50 value and the maximal inhibition between two arteries. Olprinone (0.1 microM) increased the intracellular cAMP level in the renal arterial smooth muscle cells (ASMCs) but not in the carotid ASMCs. The expression of PDE3A was greater (P = 0.008) in the carotid ASMCs than the renal ASMCs. CONCLUSION: The enhanced vasodilator action of olprinone in the renal artery is presumably because of its ability to stimulate the cAMP production, which might be attributable to the heterogeneous expression of PDE3A.
Authors: P K Smith; R I Krohn; G T Hermanson; A K Mallia; F H Gartner; M D Provenzano; E K Fujimoto; N M Goeke; B J Olson; D C Klenk Journal: Anal Biochem Date: 1985-10 Impact factor: 3.365