II. Slow oscillations in vaginal blood flow: regulation of vaginal blood flow patterns in rat by central and autonomic mechanisms.
BACKGROUND
A new method for assessing female sexual arousal through changes in slow oscillatory patterns in vaginal blood flow was first described in the previous manuscript [1]. This method was translational and discriminated between normal healthy volunteers and women with female sexual arousal disorder.


OBJECTIVE
These studies addressed the influence of autonomic and central nervous systems on slow vaginal blood flow oscillations in rats.


METHODS
Vaginal blood flow oscillations were measured in urethane-anesthetized rodents using laser Doppler flowmetry. Acquired data were filtered for frequency analysis range of 0.013-2.5 Hz.


METHODS
Data were assessed for changes in a high frequency range (HF = 0.6-2.5 Hz), and low frequency range (LF = 0.013-0.6 Hz).


RESULTS
The basal HF oscillatory component of vaginal blood flow was primarily vagally mediated, although could be modulated pharmacologically with p-chloroamphetamine in the absence of vagal innervation. The LF component could be modulated by antagonists of noradrenergic receptors but did not appear to be dependent upon tonic activation of sympathetic circuitry. The non-selective dopamine receptor agonist apomorphine induced changes in vaginal blood flow oscillations consistent with sexual arousal during metestrus in the presence of the peripheral antagonist domperidone but not in the presence of the centrally acting antagonist haloperidol. Electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus induced an anti-arousal response in vaginal blood flow oscillations. These data demonstrated that manipulation of the central nervous system alone (via centrally acting apomorphine or electrical stimulation of the PVN) could produce either a pro-arousal or an anti-arousal response in vaginal blood flow oscillations. Alterations in the LF/HF ratio measured from vaginal laser Doppler flowmetry were independently regulated from vasculature in the trunk, the tongue, and electrocardiogram-derived heart rate variability, and were independent of overall vasocongestion of the vagina as measured by mean blood flow.


CONCLUSIONS
These data indicated that slow oscillations in vaginal blood flow from rodents may be utilized as an animal model of female sexual arousal. Changes in these oscillations are driven by the central nervous system and modulated by the autonomic nervous system.
Allers
Kelly A
KA
Pfizer Global Research and Development-Genitourinary Therapeutic Area, Sandwich, UK.
Richards
Natalie
N
Scott
Liam
L
Sweatman
Catherine
C
Cheung
Jolenta
J
Reynolds
David
D
Casey
James H
JH
Wayman
Chris
C
D000818:Animals; D001058:Apomorphine / Q000627:therapeutic use*; D001341:Autonomic Nervous System / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D017078:Laser-Doppler Flowmetry; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D020018:Sexual Dysfunctions, Psychological / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D014621:Vagina / Q000098:blood supply* / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D018491:Dopamine Agonists; D014665:Vasodilator Agents; D011433:Propranolol; D001058:Apomorphine