Prostaglandins participate in the late phase of the vascular response to acetylcholine iontophoresis in humans

Abstract

The participation of prostaglandins (PGs) in the cutaneous vasodilatation to acetylcholine (ACh) applied via iontophoresis is under debate. Using laser Doppler flowmetry, we studied the long lasting effect (20 min) of iontophoretic application (30 s; 0.1 mA) of ACh on the human forearm. Experiments were repeated (1) using deionized water instead of ACh to test the effect of current application, (2) after scopolamine treatment to inhibit muscarinic cholinergic receptors, and (3) 2 h, 3 days and 10 days following inhibition of PG synthesis with aspirin or a placebo control. Cutaneous vascular conductance (CVC) was calculated at rest (CVC(rest)), at peak vasodilatation in the first 5 min following ACh iontophoresis (CVC(peak)), and 20 min after iontophoresis (CVC(20)). The minimal CVC (CVC(min)) following iontophoresis was also determined. Cutaneous response to ACh displayed a biphasic pattern with an early and transient peak (CVC(peak): 62 +/- 8% of the maximal CVC induced by local heating (MVC)) followed by a long lasting slower vasodilatation (CVC(min): 44 +/- 6; CVC(20): 56 +/- 5%MVC). The current itself had no major effect. Scopolamine almost abolished both phases. The long lasting phase was aspirin sensitive but not the transient phase. At hour 2 post-aspirin, CVC(peak) was 61 +/- 10, CVC(min) 26 +/- 6 and CVC(20) 29 +/- 6%MVC. At day 3, CVC(peak) was 53 +/- 9, CVC(min) 22 +/- 3 and CVC(20) 25 +/- 4%MVC. At day 10, CVC(peak) was 67 +/- 10, CVC(min) 47 +/- 7 and CVC(20) 50 +/- 8%MVC. Placebo had no effect. We conclude that PGs participate in the vasodilator response following ACh iontophoresis. Previous non-steroidal anti-inflammatory drug treatments must be taken into account when studying the effect of ACh iontophoresis.

Figure 1. Illustration of the different points analysed on the laser Doppler flowmetry signals

Data presented are the mean response ±s.e.m. (n = 8) observed before, during and after an ACh iontophoretic administration (30 s; 0.1 mA) at the forearm skin level. Results are expressed as a percentage of the maximal cutaneous vascular conductance (%MVC) observed after a 25-min local heating period (44°C). The white arrow indicates the period of ACh iontophoresis. Note the biphasic response to ACh iontophoresis with an early peak in CVC followed by a slow and long-lasting vasodilatation.

Figure 2. Typical cutaneous vascular response to the iontophoretic application of ACh (30 s; 0.1 mA) in forearm skin

From top to bottom, recordings are: SkBF under the ‘active’ electrode where the ACh iontophoresis was performed (Laser v1); systemic blood pressure monitored via Finapres (Pressure); local cutaneous temperature in the area close to the iontophoresis site (Skin Temperature); and SkBF at an unstimulated control site (Laser control).

Figure 3. Effect of muscarinic receptor inhibition by scopolamine on the cutaneous vasodilatation induced by iontophoretic administration of ACh

Results are expressed as a percentage of the maximal cutaneous vascular conductance (%MVC) observed after a 25-min local heating period (44°C).

Figure 4. Mean cutaneous vascular conductance (CVC) observed before, during and 20 min following the ACh iontophoresis (30 s; 0.1 mA), at different intervals from aspirin (bottom graphs) or placebo (top graphs) treatment: hour 2 (H2), day 3 (D3) and day 10 (D10)

Results are expressed as a percentage of the maximal cutaneous vascular conductance (%MVC) observed after a 25-min local heating period (44°C). The white arrow indicates the period of ACh iontophoresis. The heating period is not presented, to simplify the graphs.