Abstract
Studies in this laboratory are designed to determine the effects of vasoconstrictor agents on the erectile response in rats. We have previously demonstrated that the vasoconstrictor effect of endothelin-1 (ET-1) is sharply reduced by erection and by nitric oxide (NO) administration. The present study was performed to determine if vasoconstriction, resulting from α-adrenergic stimulation, is altered by erection and NO. During continuous monitoring of corpus cavernosum pressure (CCP) and mean arterial pressure (MAP), erection was induced by electrical stimulation of the autonomic ganglion for the innervation of the penis. When the α-adrenergic agonist methoxamine (METH, 10 μg/kg) was injected before erection (ie, into the non-erect penis), the subsequent erectile response (CCP/MAP) was significantly reduced from 0.68±0.03 before METH to 0.34±0.08 after METH. Injection of METH into the erect penis (ie, during erection) reduced the vasoconstrictor action of METH; CCP/MAP was 0.74±0.02 before METH and 0.55±0.05 after METH (P<0.05). The vasoconstrictor action of METH was slightly reduced when given in conjunction with NOR-1, a NO donor drug; CCP/MAP was 0.70±0.05 before METH, 0.55±0.09 after METH but this change was not significant. These results demonstrate that the response to α-adrenergic stimulation is attenuated during erection in response to ganglionic stimulation. Furthermore, it appears that NO, produced during erection, may serve to override agonist-induced vasoconstriction. These results support our hypothesis that NO acts to directly stimulate relaxation of cavernous smooth muscle and to inhibit the vasoconstrictor actions of agents like ET-1 and α-adrenergic agonists including norepinephrine.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 8 print issues and online access
$259.00 per year
only $32.38 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cellek S, Moncada S . Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: a comparison with other species. Proc Natl Acad of Sci USA 1997 94, 8226–8231
Guiliano F, Rampin O, Benoit G, Jardin A . The peripheral pharmacology of erection. Prog Urol 1997 7, 24–33
Melis MR, Argiolas A . Role of central nitric oxide in the control of penile erection and yawning. Prog Neuropsychopharmacol Biol Psychiatry 1997 21, 899–922
Rosselli M, Keller PJ, Dubey RK . Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 1998 4, 3–24
Andersson KE . Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 1993 45, 253–308
Hedlund P, Alm P, Andersson KE . NO synthase in cholinergic nerves and NO-induced relaxation in the rat isolated corpus cavernosum. Br J Pharmacol 1999 127, 349–360
Bloch W et al. Evidence for the involvement of endothelial nitric oxide synthase from smooth muscle cells in the erectile function of the human corpus cavernosum. Urol Res 1998 26, 129–135
Andersson KE, Stief CG . Neurotransmission and the contraction and relaxation of penile erectile tissues. World J Urol 1997 15, 14–20
Ari G, Vardi Y, Hoffman A, Finberg JP . Possible role for endothelins in penile erection. Eur J Pharmacol 1996 307, 69–74
Francavilla S et al. Endothelin-1 in diabetic and nondiabetic men with erectile dysfunction. J Urol 1997 158, 1770–1774
Zhao W, Christ GJ . Endothelin-1 as a putative modulator of erectile dysfunction. II. Calcium mobilization in cultured human corporal smooth muscle cells. J Urol 1995 154, 1571–1579
Garcia-Reboll L, Mulhall JP, Goldstein I . Drugs for the treatment of impotence. Drugs & Aging 1997 11, 140–151
Stief CG, Noack T, Andersson KE . Signal transduction in cavernous smooth muscle. World J Urol 1997 15, 27–31
Andersson KE, Wagner G . Physiology of penile erection. Physiol Rev 1995 75, 191–236
Dai Y et al. Receptor-specific influence of endothelin-1 in the erectile response of the rat. Am J Physiol Regulatory Integrative Comp Physiol 2000 279, R25–R30
Mills TM et al. Erection modulates the endothelin-1 effects on the rat penis. Int J Impot Res 2000 12, (Suppl 2): S22 (abstract)
Mills TM, Lewis R, Stopper VS, Wingard CJ . The vaso-constrictor effect of endothelin-1 in the penis is overridden during erection. J Androl 2000 March/April, (Suppl): 71 (abstract)
Traish A, Kim NN, Moreland RB, Goldstein I . Role of alpha adrenergic receptors in erectile function. Int J Impot Res 2000 12, (Suppl 1): S48–S63
Cellek S . Nitergic-noradrenergic interaction in penile erection: a new insight into erectile dysfunction. Drugs of Today 2000 36, 135–146
Reilly CM, Stopper VS, Mills TM . Androgens modulate the alpha-adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum. J Androl 1997 18, 26–31
Reilly CM, Zamorano P, Stopper VS, Mills TM . Androgenic regulation of NO availability in rat penile erection [see comments]. J Androl 1997 18, 110–115
Mills TM, Stopper VS, Wiedmeier VT . Effects of castration and androgen replacement on the hemodynamics of penile erection in the rat. Biol Reprod 1994 51, 234–238
Mills TM, Wiedmeier VT, Stopper VS . Androgen maintenance of erectile function in the rat penis. Biol Reprod 1992 46, 342–348
Jara J, Moncada I, Bueno G, Hernandez C . Intracavernous methoxamine in the treatment of priapism. Int J Impot Res 1998 10, 257–259
Muruve N, Hosking DH . Intracorporeal phenylephrine in the treatment of priapism [see comments]. J Urol 1996 155, 141–143
Kita Y et al. FR144420, a novel, slow, nitric oxide-releasing agent. Eur J Pharmacol 1995 275, 125–130
Winer BJ . Statistical Principles in Experimental Design McGraw-Hill: New York 1971 907
Tong YC, Cheng JT . Subtyping of alpha1-adrenoceptors responsible for the contractile response in the rat corpus cavernosum. Neuroscience Letters 1997 228, 159–162
Traish AM et al. A heterogeneous population of alpha 1 adrenergic receptors mediates contraction of human corpus cavernosum smooth muscle to norepinephrine. J Urol 1995 153, 222–227
Veronneau-Longueville F et al. Expression of alpha 1 adrenoceptor subtypes in rat corpus cavernosum. Int J Impot Res 1998 10, 187–194
Yoshida M et al. The possible effect of nitric oxide on relaxation and noradrenaline release in the isolated rabbit urethra. Eur J Pharmacol 1998 357, 213–219
Saenz DT, Kim NN, Goldstein I, Traish AM . Regulation of pre-synaptic alpha adrenergic activity in the corpus cavernosum. Int J Impot Res 2000 12, (Suppl 1): S20–S25
El-Mas MM, Daabees TT, El-Gowelli HM, Abdel-Galil AG . Enhanced endothelial nitric oxide activity contributes to the reduced responsiveness of vascular alpha 1-adrenoceptors following aortic barodenervation. Eur J Pharmacol 1997 337, 235–243
Cederqvist B, Gustafsson LE . Modulation of neuroeffector transmission in guinea-pig pulmonary artery and vas deferens by exogenous nitric oxide. Acta Physiol Scand 1994 150, 75–81
Lincoln TM et al. The nitric oxide-cyclic GMP signaling system. In: Bárány M (ed.) Biochemsitry of Smooth Muscle Contraction Academic Press, Inc.: San Diego 1996 257–268
Simonsen U et al. Prejunctional alpha 2-adrenoceptors inhibit nitrergic neurotransmission in horse penile resistance arteries. J Urol 1997 157, 2356–2360
Acknowledgements
We wish to thank Ms Vivian Stopper and Heather Branam for their technical assistance. This work was supported by grants from the Southeast Region American Heart Association (GIA 9960075 V) and the American Health Assistance Foundation National Heart Foundation (H 2000011) to CJ Wingard.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wingard, C., Lewis, R. & Mills, T. Erection and NO override the vasoconstrictive effect of α-adrenergic stimulation in the rat penile vasculature. Int J Impot Res 13, 212–220 (2001). https://doi.org/10.1038/sj.ijir.3900688
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijir.3900688
Keywords
This article is cited by
-
Vasoconstriction and vasodilation in erectile physiology
Current Urology Reports (2002)