Muscarinic receptor subtypes mediate vasorelaxation in isolated horse deep dorsal penile vein.

OBJECTIVES

To investigate the effect of acetylcholine (ACh) on horse deep dorsal penile vein and to characterize the muscarinic receptor subtypes involved in this response.

METHODS

Vein rings were mounted in an organ bath chamber, and the isometric tension was recorded.

RESULTS

In phenylephrine-contracted veins, ACh (1 nM to 1 microM) induced endothelium-dependent relaxation. The muscarinic receptor antagonist, atropine, produced parallel rightward shifts of the ACh response curves (pA2 = 10.04; pK(B) = 9.98). Carbachol (10 nM to 100 microM) also evoked relaxation in the vein segments, but showed a lower potency and similar relaxation to that induced by ACh. Pirenzepine, the high, intermediate, and low-affinity antagonist for M1, M3, and M2 receptors, respectively, inhibited ACh and carbachol-induced relaxation, yielding pA2 values of 7.51 and 7.37, and pK(B) values of 7.38 and 7.28, respectively. Methoctramine, a high-affinity M2 antagonist, showed no significant effect on the response to ACh. However, a high-affinity M3 antagonist, pFHHSiD, potently blocked the relaxation induced by carbachol and ACh, yielding pA2 and pK(B) values of 7.72 and 7.70 for pFHHSiD against ACh, respectively, and of 7.77 and 7.65 against carbachol, respectively.

CONCLUSIONS

These results indicate that ACh induces an endothelium-dependent relaxation in horse deep dorsal penile vein. The antagonist profile suggests that M3 muscarinic receptors mediate ACh-induced relaxation in this tissue.