Androgens and penile erection: a review.
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Androgens↗
Biomedical subjects
T M Mills
Publications and source records attributed to T M Mills.
Androgens modulate the alpha-adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum.
Rat penile erection is an androgen-dependent process with castration leading to a loss of potency. The present study was designed to determine if one of the mechanisms by which androgens maintain the erectile response is the regulation of the alpha-adrenergic responsiveness of cavernosal smooth muscle. Electrical stimulation of the major pelvic ganglion (MPG) was used to elicit erection in untreated, castrated rats (CASTRATE) or castrated rats given testosterone replacement (TESTO). The effects of phenylephrine (an alpha 1-adrenergic agonist) and prazosin (an alpha 1-adrenergic antagonist) on the erectile response were investigated. Phenylephrine, when administered to both TESTO and CASTRATE animals during erection, resulted in a dose-dependent decrease in the intracavernosal pressure (CCP) with an ED50 value of 1.8 +/- 0.48 micrograms/kg BW for TESTO rats; in the CASTRATE animals, the ED50 was significantly reduced to 0.29 +/- 0.08 microgram/kg BW. The increases in mean arterial pressure (MAP) resulting from phenylephrine injection in TESTO and CASTRATE animals were of similar magnitude and were not significantly different. Prazosin administration resulted in an enhancement of the erectile response in CASTRATE but not in TESTO animals. Taken together these results demonstrate that the cavernosal vasculature in CASTRATE animals possesses increased reactivity to alpha-adrenergic stimulation as compared to the sensitivity in TESTO rats. Based on these findings, we conclude that one of the mechanisms by which androgens maintain erectile function is by regulating the alpha 1-adrenergic responsiveness of the cavernosal smooth muscle.
Adrenergic alpha-Agonists↗
Androgenic regulation of NO availability in rat penile erection.
Prior studies from this laboratory, using untreated castrated (CASTRATE) rats and testosterone-treated castrated (TESTO) rats, have shown that the magnitude of the intracavernosal pressure increase during erection is androgen dependent. Studies from this and other laboratories have also presented evidence suggesting that penile erection is mediated principally by nitric oxide (NO). The present report was designed to confirm that androgens maintain the availability of cavernosal NO and to determine if this androgenic action is exerted at the genomic level modulating the expression of the neuronal form of the nitric oxide synthase gene (nNOS). The results showed that administration of supplemental L-arginine failed to augment the erectile response in either group, suggesting that substrate availability is not a cause of the reduced response in CASTRATE animals. Inhibition of NO synthesis with a nitro-arginine competitive inhibitor of nitric oxide synthase enzyme protein (NOS) resulted in strong inhibition of erection in both TESTO and CASTRATE rats. When given in conjunction with ganglionic stimulation to induce erection, the NO releasing drug, sodium nitro-prusside (SNP), increased intracavernosal pressure in CASTRATE rats but not in TESTO rats, suggesting a deficiency of the available NO in CASTRATE-animals. Finally, reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that mRNA levels for the enzyme nNOS in the penis were greater in TESTO animals than in CASTRATE rats. These results support the hypothesis that androgens mediate the erectile response in the rat penis by stimulating the expression of the neuronal isoform of nitric oxide synthase, thus maintaining an adequate supply of NO.
Analysis of Variance↗
Intranasal lidocaine for migraine and cluster headaches.
While lidocaine may not be effective for the relief of all cluster or migraine headaches and the pain may recur in some patients, this therapy may offer an important therapeutic alternative for certain migraine patients. Further research may provide more information, such as which headache types best respond to lidocaine, if higher concentrations of lidocaine are more effective, if lidocaine solution is more effective than lidocaine nose spray, and if other local anesthetics are as effective.
Administration, Intranasal↗
Androgenic maintenance of the rat erectile response via a non-nitric-oxide-dependent pathway.
Prior studies have demonstrated that the erectile response in the rat penis is androgen dependent and is mediated by nitric oxide (NO), the neurotransmitter synthesized by the enzyme nitric oxide synthase (NOS). The present studies used L-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, to determine if androgens also regulate alternative pathways leading to the erectile response but not mediated by NO. Castrated rats that were treated with L-NAME (L-NAME CASTRATE) exhibited little or no increase in intracavernosal pressure in response to stimulation of the major pelvic ganglion. This ganglion controls blood flow into the penis and, when stimulated, normally leads to erection. However, when castrated animals were treated with testosterone along with L-NAME (L-NAME TESTO), the animals responded to the ganglionic stimulation with increased intracavernosal pressure. This finding suggests that there are other androgen-dependent pathways that lead to penile erection but are not mediated by NO. Erection occurred in both L-NAME CASTRATE and L-NAME TESTO rats in response to intracavernosal injection of sodium nitroprusside (an NO donor drug), proving that the NO responsive mechanisms were unaffected by the inhibition of NOS activity. To investigate further the nature of this NO independent pathway, L-NAME CASTRATE and L-NAME TESTO rats were treated with either zaprinast (a specific phosphodiesterase 5 inhibitor), which would block the breakdown of cGMP to 5'GMP, or methylene blue (an inhibitor of guanylate cyclase) to prevent the synthesis of cGMP. Zaprinast treatment led to increased erectile response in L-NAME TESTO rats but not in L-NAME CASTRATE rats, demonstrating that androgen-sensitive alternative pathways increased guanylate cyclase activity. Methylene blue inhibited the erectile response in all treatment groups, showing that cyclic GMP is critical to the NO-independent pathway as well as the NO-dependent pathway. Taken together, these results support the hypothesis that androgens maintain the erectile response by alternate pathways, including one that is independent of NO but involves the synthesis of cyclic GMP.
Androgens↗
The loss of alpha-adrenergic effect during the erectile response in the long-term diabetic rat.
The present study was designed to investigate the effect of long-term, streptozotocin-induced diabetes on the erectile response in the laboratory rat. Mean arterial blood pressure (MAP) and intracavernosal blood pressure within the erectile tissue (CCP) were continuously monitored during erection elicited by stimulation of the autonomic innervation of the penis. MAP and CCP were also measured during administration of two drugs: nitroglycerin, a nitric oxide donor drug and phenylephrine, an alpha-adrenergic agonist. The results of these studies show that during graded electrical stimulation of the ganglion, the overall magnitude of the erectile response was greater in the diabetic rats than in untreated control animals. Neither diabetic nor control animals responded significantly to infusion of nitroglycerin. However, diabetic rats and control rats responded very differently to administration of phenylephrine; in the control rats, this alpha agonist caused a sharp decline in CCP as the cavernosal vessels constricted in response to the drug. The same dose of phenylephrine had no discernible effect on CCP in the diabetic animals. This loss of alpha responsiveness may be confined to the penile circulation because MAP was elevated to approximately the same extent in both groups. Taken together, these results show that long-term diabetes leads to a failure of alpha-adrenergic responsiveness in the cavernosal circulation. The greater erectile response to ganglionic stimulation in the diabetic animals is likely due to the loss of response to endogenous norepinephrine.
Adrenergic alpha-Agonists↗