Increase In Vaginal Blood Flow Research Articles

(081) Comparing the Contributions of Nitric Oxide and Estrogen to Methamphetamine-Induced Alterations of Vaginal Blood Flow in Rats

Abstract Introduction Vaginal dryness is a frequent complaint, especially in post-menopausal women. The physiology underlying the production of vaginal lubrication in response to arousing stimuli is established; however, no current pharmacological agents successfully target mechanisms utilizing this physiology. Previous research from our lab has demonstrated that female methamphetamine (meth) users experience the production of excessive vaginal lubrication immediately following an intravenous injection of methamphetamine, and we have recapitulated this in an anesthetized rodent model. We have also found that this vaginal lubrication, as well as vaginal blood flow increased by meth, are heavily nitric oxide dependent. Objective The purpose of the current study is to determine if increased vaginal blood flow correlates with increased vaginal lubrication in response to meth, and to determine if alterations in this blood flow are dependent upon nitric oxide, estrogen, or both. Methods Adult female Wistar rats were implanted with chronic indwelling jugular catheters and allowed at least one week to recover from surgery. Rats anesthetized with isoflurane gas were intravenously infused with meth or saline via the implanted catheter. Vaginal blood flow, measured using a Periflux System 5000 and a small laser probe inserted 5-10 mm into the vaginal canal, was continuously recorded before and for at least twenty minutes following drug administration. After establishing meth-induced alterations in vaginal blood flow, rats were pre-treated with L-NG-Nitro arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or fulvestrant, an estrogen receptor antagonist, followed by meth administration using the same procedure for measuring blood flow to determine the contribution of nitric oxide and estrogen. Results Meth immediately increases vaginal blood flow, followed by a decrease in perfusion, which is characteristic of a drug that induces such profound sympathetic activation. L-NAME reduced meth-induced increases in vaginal blood flow, and we predict that fulvestrant will be less effective. Conclusions Nitric oxide and estrogen are molecules critical to the production of vaginal lubrication. Nitric oxide, important for the vasodilation cascade leading to the production of vaginal transudate, contributes to meth-induced increases in vaginal blood flow and vaginal lubrication. Estrogen signaling likely contributes to meth-induced increases in vaginal blood flow, and thus, vaginal lubrication, but not as substantially as nitric oxide, making nitric oxide a better potential target for those suffering from vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Embera NeuroTherapeutics & JanOne, both affiliations unrelated to current research

Methamphetamine-Induced Alterations of Vaginal Blood Flow in Rats

ABSTRACT Introduction Those suffering with vaginal dryness, whether experienced once or chronically, frequently experience painful and unpleasurable sexual experiences and diminished self-esteem as a result. Although the physiology of vaginal transudate production is long established, no pharmacological treatment other than estrogen has shown promise in attenuating vaginal dryness. Previously, our lab has shown that methamphetamine (meth) induced vaginal lubrication in adult women and anesthetized rats. The production of these vaginal secretions was shown to be dose-, as well as nitric oxide-dependent. As the secretion of vaginal lubrication is immensely dependent on local hemodynamics and the resulting increased blood flow to the genital tissues, determining meth-induced alterations in blood flow to these tissues is paramount. Objective The purpose of the current study is to determine if increased vaginal blood flow correlates with increased vaginal lubrication in response to meth, and to determine if alterations in this blood flow are nitric oxide-dependent. Methods Adult female Wistar rats were implanted with chronic indwelling jugular catheters and allowed at least one week to recover from surgery. Rats anesthetized with isoflurane gas were intravenously infused with meth (0.06-0.96 mg/kg) or saline via the implanted catheter. Vaginal blood flow, measured using a Periflux System 5000 and a small laser probe inserted 5-10 mm into the vaginal canal, was continuously recorded before and for at least twenty minutes following drug administration. After establishing meth-induced alterations in vaginal blood flow, pre-treatment with L-NG-Nitro arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, followed by meth administration following the same procedure for measuring blood flow allowed us to determine the contribution of nitric oxide to the observed changes in blood flow. Results Preliminary findings show that an IV infusion of meth induces an immediate increase in vaginal blood flow, followed by decreased blood flow due to vasoconstriction via increased sympathetic tone. We anticipate inhibition of nitric oxide production will reduce the increase in blood flow immediately after meth administration since this decreased vaginal lubrication in response to the same treatment. Conclusions These findings provide insight into the meth-induced vaginal lubrication we have previously reported, and that meth, whose sympathomimetic action traditionally induces vasoconstriction, produces increased blood flow in vaginal tissues, which is likely the driving force for the increased transudate produced. This advancement is critical for uncovering a mechanism that may serve as the optimal pharmacological target to treat vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Embera NeuroTherapeutics & JanOne

Phosphodiesterase type 1, calcitonin gene-related peptide and vasoactive intestinal polypeptide are involved in the control of human vaginal arterial vessels

ObjectiveThe vagina makes a major contribution to the normal female sexual response cycle. An increase in vaginal blood flow is considered a key event in the mechanism of sexual arousal. Recent research has focused mainly on the cyclic GMP pathway and phosphodiesterase type 5 (PDE5, cyclic GMP specific PDE) in the control of vaginal vascular smooth muscle, whereas only little is known on the role of other key proteins and mediators of cyclic nucleotide mediated signaling in this process. The aim of the present study was to evaluate in the human vagina, by means of immunohistochemistry, the expression and distribution of phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in relation to calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and protein gene product 9.5 (PGP 9.5). Study designSections of human vagina (full wall specimens) were incubated with antibodies directed against PDE1, CGRP, VIP, PGP 9.5 and alpha-actin, followed by exposure to fluorochrome-labelled secondary antibodies. Visualization was commenced by means of laser fluorescence microscopy. ResultsMicroscopic examination revealed a dense meshwork of PGP 9.5-positive nerve fibers innervating the sections of vaginal wall. Small vessels interspersing the tissue presented dense staining for PDE1 in their smooth musculature. Blood vessels were seen surrounded by PDE1-immunoreactive longitudinal smooth muscle fibers. The vessels were also found innervated by PGP-positive varicose nerve fibers characterized by the expression of CGRP. Some fibers presented immunosignals specific for VIP. ConclusionKey mediators of the cyclic AMP and cyclic GMP pathways are co-localized in nerves seen in close proximity to vascular smooth muscle expressing PDE1. These findings suggest that both signaling cascades are involved in the control of vaginal blood flow.

746 PHOSPHODIESTERASE TYPE 1, THE CALCITONIN-GENE RELATED PEPTIDE AND VASOACTIVE INTESTINAL POLYPEPTIDE ARE INVOLVED IN THE CONTROL OF HUMAN VAGINAL ARTERIAL VESSELS

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 2011746 PHOSPHODIESTERASE TYPE 1, THE CALCITONIN-GENE RELATED PEPTIDE AND VASOACTIVE INTESTINAL POLYPEPTIDE ARE INVOLVED IN THE CONTROL OF HUMAN VAGINAL ARTERIAL VESSELS Stefan Ückert, Matthias Oelke, Markus Kuczyk, and Petter Hedlund Stefan ÜckertStefan Ückert Hannover, Germany More articles by this author , Matthias OelkeMatthias Oelke Hannover, Germany More articles by this author , Markus KuczykMarkus Kuczyk Hannover, Germany More articles by this author , and Petter HedlundPetter Hedlund Milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1771AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The vagina contributes mainly to the normal female sexual response cycle. An increase in vaginal blood flow is considered a key event in the mechanism of sexual arousal. Recent research has focused mainly on the cyclic GMP pathway and the phosphodiesterase type 5 (PDE5, cyclic GMP-specific PDE) in the control of vaginal vascular smooth muscle. In contrast, only little is known on the role of other key proteins and mediators of the cyclic nucleotide mediated signaling in this process. The aim of the present study was to evaluate in the human vagina, by means of immunohistochemistry, the expression and distribution of the phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in relation to the calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and protein gene product 9.5 (PGP 9.5). METHODS Cryostat sections of the human vagina (full wall specimens) were incubated with antibodies directed against PDE1, CGRP, VIP, PGP 9.5 and alpha-actin, followed by exposure to fluorochrome-labelled secondary antibodies. Visualization was commenced by means of laser fluorescence microscopy. RESULTS Microscopical examination revealed a dense meshwork of PGP 9.5-positive nerve fibers innervating the sections of the vaginal wall. Small vessels interspersing the tissue presented dense staining for PDE1 in their smooth musculature while no signals were observed in the non-vascular smooth muscle. The vessels were found innervated by PGP-positive varicose nerve fibers characterized by the expression of CGRP. Some fibers also presented immunosignals specific for VIP. CONCLUSIONS Key mediators of the cyclic AMP and cyclic GMP pathways are co-localized in nerves seen in close proximity to vascular smooth muscle expressing PDE1. These findings give hint that both signaling cascades are involved in the control of vaginal blood flow. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e300 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stefan Ückert Hannover, Germany More articles by this author Matthias Oelke Hannover, Germany More articles by this author Markus Kuczyk Hannover, Germany More articles by this author Petter Hedlund Milan, Italy More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

VIP, Vagina, Clitoral and Periurethral Glans — an Update on Human Female Genital Arousal

The sexually quiescent human vagina is a just moist, potential space with a minimal blood flow and very low luminal oxygen tension. The first measurable sign of sexual arousal is an increase in the blood flow. This creates the engorged condition, elevates the luminal oxygen tension and stimulates the production of surface vaginal fluid by an increased plasma transudation that saturates the fluid reabsorptive capacity of the epithelium. The vaginal lubrication created allows painless penile penetration and coital movements. The mechanisms underlying the changes appear to be mediated by Vasoactive Intestinal Peptide (VIP). VIP is present in nerves closely applied to blood vessels in the vaginal wall. Administration of VIP either intravenously, or by subepithelial injection in the vaginal wall, increases vaginal blood flow and induces vaginal fluid production. Increases in vaginal blood flow by sexual arousal are not blocked by atropine injection indicating that cholinergic mechanisms are unimportant. All the present evidence suggests that the local vaginal release of VIP induces the vaginal changes of arousal. Discourse on vaginal and pudendal anatomy (Sevely, 1987) has proposed that the female glans of the clitoris is not the true homologue of the penile glans because it has no urethral opening. The speculative suggestion is that the true female glans is the area surrounding the urethral opening (which has no specific anatomical name). Preliminary studies indicate that the area of this tissue (periurethral glans) decreases on vaginal penile insertion and reappears on withdrawal indicating that it is moved during coitus. How important such movement is to stimulate erotic sensation and how sensitive this area is to erotic stimulation are unanswered questions.

Activation of Somatosensory Afferents Elicit Changes in Vaginal Blood Flow and the Urethrogenital Reflex Via Autonomic Efferents

We examined the effects of pudendal sensory nerve stimulation and urethral distention on vaginal blood flow and the urethrogenital reflex, and the relationship between somatic and autonomic pathways regulating sexual responses. Distention of the urethra and stimulation of the pudendal sensory nerve were used to evoke changes in vaginal blood flow (laser Doppler perfusion monitoring) and pudendal motor nerve activity in anesthetized, spinally transected female rats. Bilateral cuts of either the pelvic or hypogastric nerve or both autonomic nerves were made, and blood flow and pudendal nerve responses were reexamined. Stimulation of the pudendal sensory nerve or urethral distention elicited consistent increases in vaginal blood flow and rhythmic firing of the pudendal motor nerve. Bilateral cuts of the pelvic plus hypogastric nerves significantly reduced vaginal blood flow responses without altering pudendal motor nerve responses. Pelvic nerve cuts also significantly reduced vaginal blood flow responses. In contrast, hypogastric nerve cuts did not significantly change vaginal blood flow. Bilateral cuts of the pudendal sensory nerve blocked pudendal motor nerve responses but stimulation of the central end evoked vaginal blood flow and pudendal motor nerve responses. Stimulation of the sensory branch of the pudendal nerve elicits vasodilatation of the vagina. The likely mechanism is via activation of spinal pathways that in turn activate pelvic nerve efferents to produced changes in vaginal blood flow. Climatic-like responses (firing of the pudendal motor nerve) occur in response to stimulation of the pudendal sensory nerve and do not require intact pelvic or hypogastric nerves.

An In Vivo Rat Model to Investigate Female Vaginal Arousal Response

We established a rat model to investigate the female vaginal arousal response and the role of the nitric oxide (NO) pathway on vaginal blood flow in vivo. Vaginal blood flow changes induced by pelvic nerve stimulation (PNS) in female Sprague-Dawley rats were determined by laser Doppler flowmetry. Frequency response data were determined in each animal. In addition, changes in vaginal blood flow were measured after intravenous administration of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) or the phosphodiesterase type 5 inhibitor sildenafil in response to PNS at submaximal frequency. Changes in blood flow were evaluated by comparing the area under the curve of each response. Reproducible frequency dependent increases in vaginal blood flow were observed in response to PNS. Administration of L-NAME (a NO synthase inhibitor) resulted in significant attenuation (25.6% to 18.2% vs control at 30 minutes, p <0.00001) of the PNS induced increase in vaginal blood flow. In contrast, sildenafil administration significantly increased PNS induced vaginal blood flow (166.9% +/- 25.8% vs control at 30 minutes, p <0.00001). Our data suggest that the rat is a useful and reliable animal model for investigating the vaginal arousal response. In addition, we used this model to demonstrate the important role of the NO-cyclic guanosine monophosphate pathway in vaginal arousal.

Role of the nitric oxide-cyclic GMP pathway in regulation of vaginal blood flow.

The regulatory role of nitric oxide (NO) in vaginal perfusion remains unclear. We used specific inhibitors of enzymes in the NO-cyclic GMP (NO-cGMP) pathway and investigated their effects on vaginal blood flow in the rabbit. NO synthase (NOS) activity was similar in both the proximal and distal rabbit vagina; whereas, arginase activity was 3.4-fold higher in the distal vagina. Intravenous administration of the NOS inhibitor L-NAME resulted in a 66% reduction in genital tissue oxyhemoglobin and a 53% reduction in vaginal blood flow. This attenuation occurred despite a 20-30% increase in systemic arterial pressure. The arginase inhibitor ABH caused a 2.1-fold increase in genital tissue oxyhemoglobin and 34% increase in vaginal blood flow. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one and the phosphodiesterase type 5 inhibitor sildenafil caused in a 37% reduction and a 44% increase in vaginal blood flow, respectively. These observations suggest that the NO-cGMP pathway is an important regulator of vaginal hemodynamics.

Neurophysiology and Pharmacology of Female Genital Sexual Response

Vaginal sexual arousal is a vasocongestive and neuromuscular event controlled by facilitatory parasympathetic and inhibitory sympathetic inputs. Autonomic preganglionic parasympathetic and inhibitory sympathetic fibers to the vagina and clitoris originate in the spinal cord in the sacral parasympathetic nucleus at the sacral level and in the dorsal gray commissure and the intermediolateral cell column at the thoracolumbar level, respectively. Parasympathetic fibers are conveyed by the pelvic nerve, and sympathetic fibers are conveyed by the hypogastric nerve and the paravertebral sympathetic chain. The activity of these spinal nuclei is controlled by descending projections from the brain and sensory afferens (conveyed in the pudendal, hypogastric, pelvic, and vagus nerves) from the genitalia. A key but unresolved issue concerns the neurotransmitters involved in the control of genital sexual arousal. At the peripheral level, acetylcholine plays a minor role in the regulation of vaginal blood flow, however, recent data suggests that it may be involved in the control of vaginal smooth muscle contractions. Vasoactive intestinal peptide and nitric oxide may be responsible for the increase in vaginal blood flow during sexual arousal, whereas noradrenaline is likely inhibitory. Within the central nervous system, serotoninergic projections from the brain to the spinal cord likely inhibit the induction of genital arousal by peripheral infor mations (spinal reflex). Although some neurotransmitters regulating the display of sexual behavior have been identified (for example, dopamine), their involvement in the control of genital sexual arousal has not been invested. Anatomical and electrophysiological data point to a contribution of the paraventricular nucleus of he hypothalamus and the median preoptic area, respectively, as key elements in the control of genital arousal. The recent development of models allowing the assessment of vaginal sexual arousal in anesthetized female rats should assist in deciphering the neurochemical pathways controlling vaginal sexual arousal and the development of suitable pharmacological treatment for female sexual dysfunctions.

The effects of tibolone on vaginal blood flow, sexual desire and arousability in postmenopausal women

Aims: To compare the effects of 3 months' tibolone treatment with the effects of placebo on sexual function (in particular, vaginal blood flow, and sexual desire and arousability) and climactericsymptoms in postmenopausal women.Methods: A randomized, double-blind, cross-over study was conducted in 38 postmenopausal women who received tibolone 2.5 mg/day and placebo. Vaginal blood flowduring erotic stimulation by fantasy and film was measured using a vaginal photoplethysmograph and subjects completed sexual function questionnaires and daily diaries.Results: Tibolone significantlyincreased baseline vaginal pulse amplitude (VPA) levels compared with placebo. There were significant treatment differences in VPA in favor of tibolone during fantasy periods but not during erotic filmstimulation. Tibolone was associated with significant increases in sexual desire, and the frequency of arousability and of sexual fantasies compared with those with placebo. Vaginal lubrication was significantlyimproved on tibolone. Twenty-five of 38 (66%) subjects correctly guessed when they were on active treatment. Tibolone was well tolerated.Conclusions: Tibolone was associated with significantimprovements in sexual function in postmenopausal women, reflecting both its estrogenic and androgenic properties. There were significantly greater increases in vaginal blood flow with tibolone in responseto erotic fantasy but not film, suggesting two possible pathways of female sexual response.

Vaginal and reproductive system treatments using a bioadhesive polymer

Polycarbophil, a lightly cross-linked polyacrylic acid, can remain on vaginal tissue for 3–4 days and hence serve as a platform for drug delivery. Intrinsic properties of the polymer such as acidic pKa and polyelectrolyte nature of the ionized form of the polymer can alter the local pH and hydration level of the tissue to effectively treat local pathologies. Clinical assessment of local tissue pH, in postmenopausal women, shows a reduction in pH from about 6 to 4 and maintenance of this acidic pH for about 3–4 days after the last dose. This acidic pH is an unfavorable environment for pathogens. In addition a low viscosity gel of the polymer is an effective treating agent for dry vagina, a common condition of postmenopausal females and those female cancer patients on estrogen blockers. Hydration of the vaginal tissue occurs through an increase in vaginal blood flow as determined by a laser Doppler study. In addition, the polymer appears to be an effective delivery system for the spermicidal/antiviral agent nonoxynol-9. By virtue of its ability to adhere to vaginal tissue while retaining nonoxynol-9 in its gel structure, it is an excellent extended effect spermicide. Moreover, the ability of the polymer to attach to lymphocytes, while carrying nonoxynol-9, makes it a targeted drug delivery system and useful as an AIDS prophylaxis, as well as a treating agent for other sexually transmitted diseases. Finally, employing the polymer gel with natural progesterone allows extended vaginal delivery ot the drug to achieve the clinical endpoint of a fully secretory endometrium with low serum levels of the drug. The lower serum drug levels translate into reduced side effects.

Peptide histidine methionine (PHM) increases vaginal blood flow in normal women

The effect of increasing doses of PHM given subepithelially or intravenously on vaginal blood flow was studied. Vaginal blood flow was measured by a heated oxygen electrode, and the concentration of PHM in peripheral plasma was monitored radioimmunochemically. Injection of PHM induced a significant dose-dependent increase in vaginal blood flow. The flow values correlated with the plasma concentrations independent of the way of administration. The efficacy was the same as previously found for VIP but the potency of subepithelially injected PHM was found to be 10-fold lower than that of VIP. In conclusion, PHM and VIP seem to have similar vasodilatory effects upon vaginal blood flow.

VASOACTIVE INTESTINAL POLYPEPTIDE AND HUMAN VAGINAL BLOOD FLOW: COMPARISON BETWEEN TRANSVAGINAL AND INTRAVENOUS ADMINISTRATION

1. The present study was performed to examine and compare the effect of increasing doses of vasoactive intestinal polypeptide (VIP) on vaginal blood flow following vaginal subepithelial and intravenous injection in normal women. 2. Local vaginal blood flow was measured by a heated oxygen electrode. 3. Peripheral blood samples were collected throughout the experiments for VIP analysis by radioimmunoassay. 4. Both subepithelial and intravenous injections induced a significant and dose-dependent increase in vaginal blood flow (P less than 0.05), displaying the same efficacy, potency and sensitivity. 5. The vaginal flow values correlated with the corresponding plasma VIP concentrations after both routes of administration. 6. The systemic vascular side effects; that is, flushing, hypotension and tachycardia, were observed following both subepithelial and intravenous injection. 7. The findings indicate that the effect of VIP on vaginal blood flow irrespective of route of administration is part of a systemic vasodilatory effect rather than a local response.

Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women

The human vagina is known to be heavily innervated by vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres. In the present study we have examined the effect of VIP (900 pmol × kg −1 × h −1, IV during 30 min) on vaginal lubrication and blood flow in fourteen normal non-pregnant women. Vaginal blood flow was measured by the heat clearance technique and the vaginal lubrication quantified by the weight gain of preweighed filter papers placed on the surface of the vaginal wall for 30 min. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral blood were monitored. VIP (median concentrations of 200–300 pmol × 1 −1) induced a significant increase in vaginal blood flow accompanied by a 100% increase in vaginal lubrication (from 27 mg/cm 2 to 53 mg/cm 2). The VIP infusion lead to a significant increase in pulse frequency and a significant fall in diastolic arterial blood pressure. The findings suggest that VIP may participate in the control of the local physiological changes observed during sexual arousal: genital vasodilation and increase in vaginal lubrication.

Orgasm in women in the laboratory?quantitative studies on duration, intensity, latency, and vaginal blood flow

Sexual arousal by clitoral self-stimulation was used by healthy, young adult women volunteers (n = 28) to induce orgasm in the laboratory. The duration of the orgasm was obtained using the subject's verbal indication of its start and finish. The estimated duration and the subjective experience of the orgasm self-graded on a 5-point scale were also obtained in a number of subjects. Vaginal blood flow was assessed by the power consumption needed to keep a heated oxygen electrode, held on the vaginal wall by suction, at a constant temperature. The mean measured orgasm duration was 19.9 seconds (SD, +/- 12, n = 26). For 14 subjects, their estimate of the duration of their orgasms (12.2 +/- 9.8 seconds, mean +/- SD) was greatly underestimated compared with the measured duration (26 +/- 14.6 seconds). This result indicates that data obtained on the duration of orgasm from questionnaires or interviews have suspect validity. The measured duration of the orgasms was not significantly correlated with the subjective grading. The increase in vaginal blood flow at orgasm was not significantly correlated with the subjective gradings of orgasm (n = 18), the orgasm latency (time taken to induce orgasm, n = 18), or the measured duration of orgasm (n = 14).

Vasoactive intestinal polypeptide (VIP) increases vaginal blood flow and inhibits uterine smooth muscle activity in women.

The human vagina and uterus are heavily innervated by VIP-containing nerve fibres. In the present study, we have measured vaginal blood flow, transmucosal oxygen tension and uterine smooth muscle activity during stepwise intravenous infusion of vasoactive intestinal polypeptide (VIP) (0, 100, 300, 900 pmol kg-1 h-1) in non-pregnant women. Vaginal blood flow was measured by the heat clearance technique, transmucosal oxygen tension by an O2-electrode and uterine activity by a micro-tip pressure catheter in the uterine cavity. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral venous blood were monitored. VIP induced a concentration-dependent increase in vaginal blood flow. The transmucosal oxygen tension was not significantly changed by VIP. The maximum dose of VIP decreased systolic as well as diastolic blood pressure and increased pulse frequency. VIP inhibited uterine activity. These findings suggest that VIP participates as a neurotransmitter in the control of genital physiological responses.

Patterns of female sexual arousal during sleep and waking: Vaginal thermo-conductance studies

The main objective of this investigation was to ascertain whether there are, in the female, periods of sexual excitation or arousal during REM sleep similar to the cycle of penile erections in the male. In a group of 10 subjects, 21–35, utilizing a thermoconductance method that gives a measure of vaginal blood flow (VBF), we are able to confirm that females manifest cyclic episodes of vascular engorgement during REMPs equivalent to erections in men. They occur with equal frequency (95% of REMPs) but differ in distribution, in greater frequency during NREM sleep, in the shorter duration of individual VBF episodes, and in the less tight linkage of VBF episodes to the REMPs. The increases in VBF, in terms of rises of the recording pen on the graph paper, varied from 10 to 45 mm. In order to ascertain the significance of these increases, we compared these sleep responses with waking VBF responses evoked by nonerotic and erotic stimuli and by masturbation. Only erotic stimuli gave VBF responses, the greatest to the movie and masturbation; these were no greater than the maximum levels attained during sleep, namely 40 to 45 mm. Maximum vascular engorgement is finite in male and female and is limited by anatomy. The fact that VBF REM increases appear to be identical to VBF responses to passive waking erotic stimulation and show similar cardiorespiratory patterns suggests that they, too, are erotic in nature. Additionally, the preliminary results of the waking experiment demonstrate that a very high percentage of VBF REM increases are associated with dreams that contain overt or symbolic sexual content. The results indicate that REM periods with VBF increases have a far greater chance of being associated with sexual dreams than do REMPs or NREMPs with minimal VBF increases.

Intravaginal prostaglandin E 1 increases vaginal blood flow

We investigated the possibility that PGE 1, at approximately the minimal seminal plasma concentration reported to be associated with human fertility (3), placed in the vaginas of female dogs might produce local vasodilation and thereby increase vaginal blood flow. Fifteen micrograms of PGE 1 in 1 ml, 38°C saline increased vaginal blood flow 2.5 times (0.27 ± 0.10 to 0.67 ± 0.10 ml/g·min) as compared to control (1 ml, 38°C saline, intravaginally) without altering arterial pressure, hepatic blood flow, or renal blood flow. We conclude that seminal fluid PGE 1 can produce vaginal vasodilation. The role of seminal fluid PG induced increases in vaginal blood flow upon reproductive success, if any, is entirely speculative.

Cold pressor test in women: Effect on vaginal blood flow

Vaginal blood flow changes in women were evaluated qualitatively by heat-flow discs mounted on a cooled vaginal probe. Statistically significant increases in vaginal blood flow, systolic blood pressure, and pulse rate were found in seven normal subjects during a 4 minute immersion of one hand in ice water.