TY - JOUR
T1 - Altered contractility of rabbit penile corpus cavernosum smooth muscle by hypoxia
AU - Kim, Noel N.
AU - Kim, Je-Jong
AU - Hypolite, Joseph
AU - García-Díaz, J. Fernando
AU - Broderick, Gregory A.
AU - Tornheim, Keith
AU - Daley, Jennifer T.
AU - Levin, Robert
AU - Saenz De Tejada, Iñigo
PY - 1996/1/1
Y1 - 1996/1/1
N2 - Purpose: To investigate the effects of severe hypoxia on trabecular smooth muscle contractility. Materials and Methods: Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. In some experiments intracellular free Ca2+ concentration and tension were measured by the intracellular fluorescent dye FURA-2 and isometric tension recording simultaneously. Results: Contractions elicited by norepinephrine, endothelin-1 or potassium were attenuated under hypoxic conditions (pO2 ~10 mm. Hg). Strips contracted with 20 mM, K+ under normoxic conditions and then exposed to hypoxia consistently lost the potassium-induced tone. The hypoxia- induced relaxation was not affected by the removal of the endothelium, by treatment with the cyclooxygenase blocker, indomethacin, or with the guanylate cyclase blocker, methylene blue. The potassium channel opener, cromakalim, and adenosine relaxed potassium contracted strips; however, the potassium channel blockers glibenclamide, apamin, barium chloride and charybdotoxin or the adenosine receptor antagonist 8-(p- sulfonyl)theophylline were unable to prevent hypoxia-induced relaxation. Tetraethylammonium, a potassium channel blocker, and the depolarizing agents ouabain and high potassium (80 mM.), partially prevented hypoxia-induced relaxation. The calcium ionophore, ionomycin, had no effect on hypoxia- induced relaxations. Hypoxia, within 2 to 6 minutes, caused a large accumulation in intracellular calcium, concomitant with a loss of trabecular smooth muscle tone. Both these effects could be reproduced by inhibiting oxidative phosphorylation with 2,4,dinitrophenol. Reoxygenation resulted in an immediate recovery of both tone and intracellular calcium levels. Tissues under hypoxic conditions for 30 minutes had a 24% and 67% decrease in the ATP/ADP ratio and in creatine phosphate concentrations, respectively. Conclusion: Hypoxia causes a simultaneous increase in intracellular calcium and relaxation which, we propose, is the consequence of inhibition of oxidative phosphorylation with loss of high energy phosphates, necessary for the homeostasis of Ca2+ and the contractile mechanism of the cavernosal smooth muscle.
AB - Purpose: To investigate the effects of severe hypoxia on trabecular smooth muscle contractility. Materials and Methods: Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. In some experiments intracellular free Ca2+ concentration and tension were measured by the intracellular fluorescent dye FURA-2 and isometric tension recording simultaneously. Results: Contractions elicited by norepinephrine, endothelin-1 or potassium were attenuated under hypoxic conditions (pO2 ~10 mm. Hg). Strips contracted with 20 mM, K+ under normoxic conditions and then exposed to hypoxia consistently lost the potassium-induced tone. The hypoxia- induced relaxation was not affected by the removal of the endothelium, by treatment with the cyclooxygenase blocker, indomethacin, or with the guanylate cyclase blocker, methylene blue. The potassium channel opener, cromakalim, and adenosine relaxed potassium contracted strips; however, the potassium channel blockers glibenclamide, apamin, barium chloride and charybdotoxin or the adenosine receptor antagonist 8-(p- sulfonyl)theophylline were unable to prevent hypoxia-induced relaxation. Tetraethylammonium, a potassium channel blocker, and the depolarizing agents ouabain and high potassium (80 mM.), partially prevented hypoxia-induced relaxation. The calcium ionophore, ionomycin, had no effect on hypoxia- induced relaxations. Hypoxia, within 2 to 6 minutes, caused a large accumulation in intracellular calcium, concomitant with a loss of trabecular smooth muscle tone. Both these effects could be reproduced by inhibiting oxidative phosphorylation with 2,4,dinitrophenol. Reoxygenation resulted in an immediate recovery of both tone and intracellular calcium levels. Tissues under hypoxic conditions for 30 minutes had a 24% and 67% decrease in the ATP/ADP ratio and in creatine phosphate concentrations, respectively. Conclusion: Hypoxia causes a simultaneous increase in intracellular calcium and relaxation which, we propose, is the consequence of inhibition of oxidative phosphorylation with loss of high energy phosphates, necessary for the homeostasis of Ca2+ and the contractile mechanism of the cavernosal smooth muscle.
KW - ATP
KW - intracellular calcium
KW - potassium channels
KW - priapism
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U2 - 10.1016/S0022-5347(01)66519-4
DO - 10.1016/S0022-5347(01)66519-4
M3 - Article
C2 - 8558723
AN - SCOPUS:9044225147
VL - 155
SP - 772
EP - 778
JO - Journal of Urology
JF - Journal of Urology
SN - 0022-5347
IS - 2
ER -