[NORADRENALINE-EVOKED RESTORATION OF THE NEUROGENIC VASOREACTIVITY DIMINISHED BY ACIDOSIS].

The effect of 0.03-1.0 µM noradrenaline on the neurogenic contractile response to electrical field stimulation of the juvenile rat tail artery segment in control conditions and after the solution pH decrease from 7.4 to 6.6 was studied. Acidosis were shown to inhibit this response significantly at all frequencies of stimulation used (3, 5, 10, and 40 Hz). Noradrenaline potentiated neurogenic vasoconstriction diminished spontaneously or by low pH. The potentiative effect of noradrenaline in acidic solution was more pronounced at higher frequencies of stimulation and noradrenaline concentrations. This phenomenon can, at least in part, account for blood flow redistribution from less important organs to vital ones during exercise which is characterized by acidosis, augmented sympathetic nerve activity and increased levels of noradrenaline.

Noradrenaline can restore decreased neurogenic vasoreactivity.

Experiments on isolated segments of the tail artery from young (aged 4-6 weeks) rats addressed the effects of noradrenaline (0.01-1.0 microM) on the reactions of these segments to stimulation with an electric field in isometric conditions. These studies showed that noradrenaline increases this reaction after spontaneous or acidosis (pH 6.6)-induced decreases and that the extent of this increase was proportional to the magnitude of the previous reduction in the reaction. The increase in the decrease in the reaction to electrical stimulation was accompanied by widening of the range of potentiating noradrenaline concentrations and an increase in the noradrenaline concentration at which potentiation was maximal. The nitric oxide synthesis blocker NG-nitro-L-arginine did not eliminate the potentiating effect of noradrenaline. These data led to the conclusion that noradrenaline produces a concentration-dependent recovery of decreased neurogenic reactivity of blood vessels and that this effect is not associated with changes in nitric oxide synthesis.

Melatonin-evoked potentiation of the juvenile rat tail artery neurogenic reactivity depends on degree of the change in the reactivity.

AIM: Dependence of the melatonin-evoked potentiation of the rat tail artery neurogenic reactivity on degree of the change in the reactivity was studied. METHOD: Electrical field stimulation-evoked contractile response of the juvenile rat tail artery segment under isometric conditions was recorded. 0.1 mum melatonin was administered after the change in the response produced both spontaneously and by acidification (pH 6.6) or alkalinization (pH 7.8) of the solution. RESULTS: During the course of experiment, the contraction force continuously declined, being reduced by 12 +/- 5, 24 +/- 7 and 32 +/- 6% at 20, 70, and 170 min after beginning of experiment, respectively. Melatonin applied at these time points increased the contraction by 20 +/- 5, 41 +/- 10, and 48 +/- 8%, respectively, relative to control. This increase in potentiating effect of melatonin during the course of experiment was not because of sensitization of the segment to the hormone. Acidosis-induced considerable decline in neurogenic contraction was counteracted by melatonin, while after alkalosis-induced augmentation in the contraction the hormone was not effective. Melatonin increased the artery response to 0.1 mum noradrenaline. CONCLUSION: These data suggest that melatonin can restore an attenuated neurogenic reactivity of the juvenile rat tail artery. The effect is more pronounced with further decrease in reactivity and might be due to a change in sensitivity of the post-junctional membrane to noradrenaline.

Melatonin restores diminished neurogenic reactivity of the juvenile rat tail artery.

The effect of melatonin on neurogenic reactivity of the juvenile rat tail artery segment was studied. The electrical field stimulation-evoked contraction of the segment decreased in the course of the experiment. Melatonin (0.1 microM) applied at different time points of the experiment produced an increase in the contraction, which directly correlated with a spontaneous decrease in the electrical field stimulation-evoked response. The increase in the potentiating effect of melatonin in the course of the experiment was not due to sensitization of the segment to this substance. Noradrenaline-evoked contraction of the vessel segment was not changed by melatonin. The data indicate that melatonin restores the diminished neurogenic reactivity of the juvenile rat tail artery probably by potentiation of the contractile response of the vessel, but this effect is hardly due to a change in sensitivity of the postjunctional membrane to noradrenaline.

Effect of pH changes on reactivity of rat mesenteric artery segments at different magnitude of stretch.

The reaction to noradrenaline (NA) (10 microM) and electrical field stimulation (EFS) was studied in rat mesenteric artery segments at different magnitude of stretch and the solution pH. Alkaline solution (pH 7.8) potentiated and acidic solution (pH 7.0 or 6.6) inhibited the EFS-evoked response of segments stretched to values corresponding to arterial pressure of 5-200 mmHg. These pH changes failed to alter resting tension at any magnitude of stretch. Acedic solution of pH 6.6 caused 2-fold decrease in noradrenaline- and 5-15-fold decrease in the EFS-evoked response of segments stretched to values corresponding to arterial pressure of 50, 125, and 200 mmHg. In segments pre-contracted with noradrenaline (10 microM) acidification caused the decrease of the dilation and appearance of the constriction induced by the EFS. The effect of acidosis on the EFS-evoked response was diminished and the effect on noradrenaline-evoked response was abolished in the presence of nitric oxide synthase blocker, NG-nitro-L-arginine (100 microM). These results suggest that acidosis effectively impairs reactivity of the rat mesenteric artery in a wide range of its stretch, and the inhibition of the response to noradrenaline occurs completely, while to EFS only partially due to nitric oxide (NO) release, presumably by the endothelium. In addition, it was shown that acidosis is able to act not only as the commonly known dilator agent, but also as an agent potentiating constriction in case of the high noradrenaline-induced tone.

Changes in reactivity of rat arteries subjected to dynamic stretch.

The effect of dynamic stretch on the reactivity of the rat tail and mesenteric artery segments was studied. Segments mounted on a myograph were stretched by a computer-controlled motorized micromanipulator. Dynamic stretch (1, 5 or 7 Hz) inhibited the artery constriction induced by noradrenaline (10 microM), 5-hydroxytryptamine (0.7 microM), or electrical field stimulation of intramural nerves. In contrast, dynamic stretch enhanced the tetrodotoxin-insensitive dilation induced by electrical field stimulation of noradrenaline-contracted arteries. Maximal increase of dilation evoked by electrical field stimulation (24.5 +/- 5.0% in mesenteric and 50.3 +/- 15.6% in the tail artery) was observed at a dynamic stretch-frequency of 5 Hz. An inhibitor of nitric oxide synthesis, NG-nitro-L-arginine (100 microM), abolished the difference in reactivity between static and dynamic conditions. The results indicate that dynamic stretch of the arteries activates nitric oxide synthesis/secretion, thus reducing constrictor and increasing dilator responses to the stimuli used.

Effects of extracellular pH on the response of the isolated rat mesenteric artery to electrical field stimulation.

In experiments on isolated segments of the rat mesenteric artery, effects of changes in solution pH on the response of the segments to noradrenaline (10 microM) or electrical field stimulation (EFS) were studied. The pH 7.8 solution slightly increased (from 0.48 +/- 0.07 mN at pH 7.4 to 0.67 +/- 0.12 mN or by 41%). while the pH 7.0 and 6.6 solutions significantly decreased (to 0.16 +/- 0.05 and 0.08 +/- 0.04 mN or by 66 and 83%, respectively) the EFS-evoked response of the vessel prestretched to the value corresponding to the intravascular pressure of about 100 mm Hg. A pH shift either to the alkaline or acidic range did not change the resting tension (15.65 +/- 0.74 mN at pH 7.4) of the vessel without precontraction. The pH 6.6 solution reduced the response to noradrenaline twofold. Dilation produced by EFS of noradrenaline-precontracted segment was inhibited and the constrictor responses appeared in the pH 6.6 solution. In the vessel pretreated with N(G)-nitro-L-arginine (100 microM), the acidification of the solution (pH 6.6) inhibited the response of the vascular segment to EFS to a lower extent and did not change its response to noradrenaline. The data obtained demonstrate an inhibitory effect of acidosis on reactivity of the rat mesenteric artery as well as a modification of this effect under a high initial tone of the vessel studied.

Hydrocortisone administration enhances vessel contractility in Koltushi low-, and Koltushi high-avoidance rats.

The contractility of tail artery rings was investigated in rats psychogenetically selected for rapid (KHA) and slow (KLA) acquisition of an avoidance response in the shuttle box. The vessel contractility was greater in the KHA rats. Hydrocortisone administration enhanced vessel contractility in both strains.