Increased vaginal blood flow is often used as a marker of female sexual arousal and yet the mechanisms controlling vaginal arteries remain largely unstudied. Investigations into the pharmacology and physiology of female sexual function have been hampered by a lack of experimental models with current studies relying on cell cultures and organ bath in vitro techniques (Traish et al. 2002). The aim was to use wire myography to allow direct measurement of contraction and relaxation mechanisms within rabbit vaginal arteries.

All experiments were carried out in compliance with UK legislation. Vaginal arteries were isolated from female NZW rabbits (~3Kg) and dissected into 2 regions, the artery entering the vagina being referred to as the ‘extra’ vaginal artery (EVA) and the artery within the lower 2cm of the vagina the ‘intra’ vaginal artery (IVA). Using the myograph technique, isometric recordings were made from 2mm vessel rings (i.d. 266 ± 8.7 µm EVA; 140 ± 3.3 µm IVA), which were equilibrated for 30 mins under a resting tension of 0.3g. All experiments were performed in the presence of Krebs at 37 °C gassed with 95% O₂ and 5% CO₂. Arterial rings were pre-contracted thrice with 10µM noradrenaline (NA) followed by a 30 min washout. Agonists were applied cumulatively and normalised as a percentage of NA contractions or agonist E_max. Antagonists were pre-incubated for 30-40 mins. All data are expressed as mean ± s.e.mean where n = number of animals. Statistical significance was determined using a one-way ANOVA.

To determine the role of adrenoceptors in the vaginal artery exogenous NA (EVA, E_max 2.65 ± 0.05g, pEC₅₀ 5.85 ± 0.04, n = 5; IVA, E_max 1.60 ± 0.03g, pEC₅₀ 6.15 ± 0.04, n = 4) and the ₁-adrenoceptor agonist phenylephrine (PE) (EVA, E_max 2.00 ± 0.10g, pEC₅₀ 5.23 ± 0.09, n = 3; IVA, E_max 1.35 ± 0.08g, pEC₅₀ 5.34 ± 0.11, n = 4) were shown to cause vasoconstriction. NA-induced vasoconstriction was shifted to the left by the presence of NA uptake blockers corticosterone (30 µM) and cocaine (3 µM) (EVA, E_max 1.92 ± 0.08g, pEC₅₀ 6.74 ± 0.10, n = 3, P < 0.05; IVA, E_max 1.64 ± 0.05g, pEC₅₀ 6.39 ± 0.06, n = 4, P < 0.05) and potentiated by the nitric oxide synthase inhibitor L-NAME in EVA (E_max 3.77 ± 0.08g, pEC₅₀ 6.20 ± 0.05, n = 4) but not IVA (E_max 1.78 ± 0.07g, pEC₅₀ 6.13 ± 0.07, n = 3). PE-induced vasoconstriction was ~80% of NA vasoconstriction and was inhibited in a competitive manner by the non-selective ₁-adrenoceptor antagonist prazosin in EVA (P < 0.05, pA 2 8.55, Hill slope 0.54 to 1.04, n = 5-6) and IVA (P < 0.05, pA₂ 8.66, Hill slope 0.32 to 0.83, n = 4-6). Interestingly, transient spontaneous relaxations were observed in tissue pre-contracted with NA, which were more evident in EVA (4 of 52 arterial rings) and abolished in the presence of L-NAME (100 µM).

To examine the role of the endothelium and nitric oxide (NO), vaginal arteries were pre-contracted with 10 µM NA and relaxed by acetylcholine (ACh) (EVA, E_max 94.4 ± 7.7%, pIC₅₀ 6.45 ± 0.18, n = 4; IVA, E_max 92.1 ± 3.7%, pIC₅₀ 6.42 ± 0.09, n = 6). L-NAME (100 µM) only partially inhibited the ACh-induced relaxation (EVA, E_max 48.4 ± 7.0%, n = 4; IVA, E_max 62.3 ± 3.9%, n = 3).

Vasoactive intestinal polypeptide (VIP) is believed to be a potent vasodilator in the vaginal tissue (Ziessen et al. 2002). VIP caused vasodilatation of 10 µM NA pre-contracted arteries (EVA, E_max 77.4 ± 4.8%, pIC₅₀ 7.86 ± 0.09, n = 6; IVA, E_max 87.4 ± 8.0%, pIC₅₀ 8.26 ± 0.19, n = 6) that was not affected by L-NAME (100 µM) (n = 2-4, P > 0.05) but was competitively inhibited by the VIP antagonist VIP (6-28) (10 µM, EVA, E_max 68.3 ± 3.9%, pIC₅₀ 7.23 ± 0.08, n = 3; IVA, E_max 82.8 ± 6.8%, pIC₅₀ 7.23 ± 0.13, n = 4).

In conclusion, wire myography is a valuable and novel approach to pharmacologically characterise vaginal arteries. The data suggests regional variation within the vaginal artery with a greater contractile response to adrenoceptor agonists in EVA, and IVA showing greater relaxation to ACh that was predominantly resistant to L-NAME. VIP was shown to be a potent vasodilator in both EVA and IVA.

Traish et al. (2002). Arch. Sex. Behav. 31, 393-400.
Ziessen et al. (2002). Br. J. Pharmacol. 135, 546-554.