Modulation of the myogenic response by neurogenic influences in rat small arteries

Abstract

The hypothesis that the amplitude of the myogenic response is modulated by factors released from nerve endings was tested in rat tail small arteries. A pressure myograph in conjunction with direct stimulation of nerve endings by electrical field stimulation (EFS) was used to determine rat small artery contractile reactions. Vessel pretreatment with 10(- 5) M phentolamine abolished EFS-induced reactions completely indicating that they are mediated mainly by an adrenoceptor agonist, probably noradrenaline. In the absence and presence of 10(- 5) M phentolamine, vessel diameter changes in the pressure range from 10 to 120 mmHg were not different. Vessel stimulation by (i) EFS, (ii) noradrenaline, (iii) selective stimulation of alpha1- and alpha2-receptors, (iv) serotonin, or (v) vasopressin significantly reduced the diameter change induced by stepping pressure from 10 to 40 mmHg compared to unstimulated, control vessels. Vessel diameter changes induced by stepping pressure from 40 to 80 and from 80 to 120 mmHg, however, were not different in vessels stimulated with EFS and noradrenaline compared to controls. In conclusion, these data show that factors released from unstimulated adrenergic nerve endings (i.e., not stimulated by EFS) are not involved in the myogenic response. In contrast, factors released upon stimulation of nerve endings can modulate the amplitude of the myogenic response, but only at low pressures. Thus, the pressure range for myogenic blood flow autoregulation is extended to lower pressures. Myogenic autoregulation of blood flow at physiological pressures is unaltered.

Figure 1

The small tail artery. Left panel: An anatomic drawing of a piece of the rat tail is shown demonstrating in the cross-section the localization of the ventral vessel channel. Right panel: Magnified schematic drawing of the localization of the vessels in the ventral vessel channel. The main ventral tail artery is located just beneath the connective tissue sheet covering the vessel channel. Below this vessel, there are two thin-walled vessels, the main ventral tail veins. Deeper in the channel, two smaller vessels, the small tail arteries, are localized. These vessels are first-order branches of the main ventral tail artery running parallel along the main tail artery.

Figure 2

Determination of conditions for a selective stimulation of nerve endings. (a) Example of the effect of electrical field stimulation (EFS) (pulse duration 0.1 ms, 20 Hz) on vessel diameter. (b) Effect of EFS on vessel diameter in the presence of 10^{− 6} M tetrodotoxin (TTX) in endothelium-intact vessels showing the existence of vessel dilations and constrictions (n=7). (c) Effect of EFS on vessel diameter in the presence of 10^{− 6} M TTX in endothelium-denuded vessels; no effect was observed (n=8, P=0.62). Compare also to Figure 4a showing the effect of EFS on vessel diameter in the absence of TTX in endothelium-denuded vessels.

Figure 3

Effect of endothelium removal on the myogenic response. (a) Effect of noradrenaline on vessel diameter in endothelium-intact (+ E) and endothelium-denuded (− E) vessels; no difference was observed (n=6, P=0.17). (b) Effect of adenosine on vessel diameter in endothelium-intact (+ E) and endothelium-denuded (− E) vessels; no difference was observed (n=4, P=0.89). (c) Effect of pressure on vessel diameter (myogenic response) in endothelium-intact (+ E) and endothelium-denuded (− E) vessels; no difference was observed (n=6, P=0.91).

Figure 4

Determination of the effect of phentolamine on EFS-induced response. (a) Effect of EFS on vessel diameter in endothelium-denuded vessels; a significant effect was observed (n=11, P<0.01). (b) Effect of EFS on vessel diameter in endothelium-denuded vessels in the presence of 10^{− 5} M phentolamine; no effect was observed (n=6, P=0.60).

Figure 5

Lack of involvement of adrenergic nerve endings not stimulated by EFS in the myogenic response. Diameter changes to the pressure steps indicated are shown in the absence (ctrl) and in the presence of 10^{− 5} M phentolamine (PHE); no differences were observed (P=0.55, P=0.90 and P=0.18, respectively).

Figure 6

Involvement of stimulated nerve endings in the myogenic response. (a) Example of the effect of a pressure change from a starting value of 10 to 40 mmHg and back to 10 mmHg on vessel diameter in the absence and presence of EFS (0.1 ms, 10 Hz, 24 mA mm^{− 2}). (b) Diameter changes in response to the pressure steps indicated below the bars in the control (ctrl), during EFS (EFS), and in the presence of noradrenaline (NA); at the step from 10 to 40 mmHg, a significantly different effect was observed during EFS and NA compared to control (both P<0.01); at the other pressure steps, no differences were found (P=0.14 and P=0.07).

Figure 7

Changes in calculated vessel tone after different pressure steps. (a) Example of the effect of a pressure change from a starting value of 10 to 40 mmHg and back to 10 mmHg on calculated tone in the absence and presence of EFS (0.1 ms, 10 Hz, 24 mA mm^{− 2}). (b) Changes of calculated tone in response to the pressure steps indicated below the bars in the control (ctrl), during EFS (EFS), and in the presence of noradrenaline (NA); at the steps from 10 to 40 mmHg and from 40 to 80 mmHg, a significantly different effect was observed during EFS and NA compared to control (P<0.05 and P<0.01, respectively); at the other pressure step, no difference was found (P=0.50). The data presented in this figure are based on the data shown in Figure 6.

Figure 8

Effect of smooth muscle cell activation on the myogenic response. (a) Diameter changes in response to a pressure step from 10 to 40 mmHg in the control (ctrl), during EFS (EFS), in the presence of noradrenaline (NA), and during selective α₁- and α₂-receptor stimulation; a significantly different effect was observed during EFS, NA application, and selective α₁- and α₂-receptor stimulation compared to control (all P<0.01). (b) Diameter changes in response to the pressure steps indicated below the bars in the control (ctrl), in the presence of serotonin (Ser) and vasopressin (Vaso); at the step from 10 to 40 mmHg, a significantly different effect was observed during Ser and Vaso compared to control (both P<0.05); at the other pressure steps, no differences were found (P=0.53 and P=0.65).