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TRYPTAMINERGIC VASOCONSTRICTION INDUCED BY ADENOSINE IN THE FEMORAL VASCULAR BED OF THE RAT
TRYPTAMINERGIC BY
ADENOSINE
VASOCONSTRICTION IN BED
Kazushige
THE OF
FEMORAL THE
INDUCED VASCULAR
RAT
SAI,~AI and Nlichitaka
AKINIA
Departinent of Pliarniacology, Research Laboratories, Chugai Pharrnaceiutical Co., Toshin'ra-ku, Tokyo 171, Japan Accepted August 5, 1977
Since Berne (1) reported that adenosine is released from the hypoxic myocardium and that it has a strong coronary vasodilating action, a considerable amount of information has been accumulated on the mode of action of this compound.
Investigations (2-4) on
dogs have shown that this compound induces a dominant vasodilatation in most peripheral vascular beds, while a vasoconstriction occurs in the renal vascular bed.
In the course of
experiments on rats we found that adenosine injected selectively into the femoral artery produced a marked and long-lasting vasoconstriction
preceded by a brief vasodilatation.
The present report is a description of the mechanism of vasoconstriction by adenosine. Five experiments were done by means of a cross-circulation technique.
Male Sprague
Dawley rats were allowed free access to food and water overnight prior to experiments. Recipient rats (300-450 g) were anaesthetized with sodium pentobarbital, and donor rats (550-650 g) initially with sodium pentobarbital, urethane 400 mg/kg s.c. about one hour later.
65 mg/kg i.p.
65 mg/kg i.p., and with
The right hind limb of the recipient was
completely isolated from the body and was perfused at a fixed flow rate through the femoral artery with heparinized blood (37 C) from the carotid artery of a donor by the use of peri staltic pump (Mitsumi Science, SJ-1210). the end of the experiments.
The pump was precalibrated and re-checked at
The perfusion pressure was adjusted to about 100 mmHg at
the start of perfusion and maintained throughout the experiment.
The blood pressure of
the donor and the perfusion pressure were continuously measured by means of an individual
FIG. 1. Effects of methysergide on the sasoeonstrictor action of 5-HT, noradrenaline (Nor) and adenosine (Ads). A) Typical recordings. Note that the perfusion pressure (PP) remained unchanged after an injection of 0.3 ;,g of methysergide. Bl Summarized data. White (control) and oblique striated (treated) colums show the peak responses (mmHg) from the corresponding pre-drug levels to adenosine, noradrenaline and 5-HT before and after methysergide, respectively. Vertical bars represent means i SE (n 5). NS, not significant. The wet weights (H W) of the perfused right hind limb were ?4.5 0.6 (body weights of the recipient, 376.0_ 31.9 g) and the perfusion flow rate 11.1 x_0.8 ml/min/100 g HW. Initial perfusion pressure, 96.0-:_42 mmHg.
pressure transducer (Nihon Kohden, RP-5).
Recordings were made on an ink-writing
polyrecorder (TOA Electronics, EPR-3T). The venous outflow from the femoral vein of the isolated limb was received by a venous reservoir and in turn returned to the jugular vein of the donor by 15 cm drop of hydrostatic pressure.
Drug solutions were prepared
freshly with 0.9% saline before use and a volume of 0.01 ml was injected into the right femoral artery of the recipient over a 4 sec period.
As the perfusion rate was constant,
changes in the perfusion pressure caused by drugs were taken as drug responses. used were as follows:
)-noradrenaline
hydrochloride
The drugs
(Sankyo), 5-hydroxytryptamine
creatinine sulphate (5-HT, Sigma), adenosine (Wako Junyaku) and methysergide tartrate (Sandoz). Values in the text are means-~--SE. Student's t-test was used for statistical analyses and P values under 0.05 were considered significant. A single injection of either 5-HT (0.3 Pg) or noradrenaline (0.1 /eg) into the femoral artery had a constrictor effect on the vascular bed.
On the other hand, adenosine (10 ,ig)
induced a biphasic response, namely a marked and long-lasting constriction preceded by a brief vasodilatation.
Methysergide (0.3 / eg) which is a potent 5-HT antagonist (5), prevented
completely the vasoconstrictor effects of adenosine as well as of 5-HT, while it did not affect that of noradrenaline (Fig. IA and B). These results suggest that adenosine induces vasoconstriction either directly by acting on the tryptaminergic receptor or indirectly by releasing 5-HT from the stores. REFERENCES 1) BERNE,R.M.: Am. J. Physiol. 204, 317 (1963): 2) HASHIMOTO, K. ANDKuMAKLRA,S.: Japan. J. Physiol. 15, 540 (1965): 3) SATOH,S. ANDHASHIMOTO, K.: Tohoku J. exp. Mcd. 110, 367 (1973); 4) SAKAI,K., SUGANO, S., TAIRA,N. ANDHASHIMOTO, K.: Japan. J. Pharmacol. 24, 659 (1974); 5) DOUGLAS, W_W.: ThePharmacological Basis of Therapeutics,Edited by GOODMAN L.S. ANDGILMAN,A., p. 622, MacMillan Publishing Co., Inc., New York (1975)
ADENOSINE
VASOCONSTRICTION IN BED
Kazushige
THE OF
FEMORAL THE
INDUCED VASCULAR
RAT
SAI,~AI and Nlichitaka
AKINIA
Departinent of Pliarniacology, Research Laboratories, Chugai Pharrnaceiutical Co., Toshin'ra-ku, Tokyo 171, Japan Accepted August 5, 1977
Since Berne (1) reported that adenosine is released from the hypoxic myocardium and that it has a strong coronary vasodilating action, a considerable amount of information has been accumulated on the mode of action of this compound.
Investigations (2-4) on
dogs have shown that this compound induces a dominant vasodilatation in most peripheral vascular beds, while a vasoconstriction occurs in the renal vascular bed.
In the course of
experiments on rats we found that adenosine injected selectively into the femoral artery produced a marked and long-lasting vasoconstriction
preceded by a brief vasodilatation.
The present report is a description of the mechanism of vasoconstriction by adenosine. Five experiments were done by means of a cross-circulation technique.
Male Sprague
Dawley rats were allowed free access to food and water overnight prior to experiments. Recipient rats (300-450 g) were anaesthetized with sodium pentobarbital, and donor rats (550-650 g) initially with sodium pentobarbital, urethane 400 mg/kg s.c. about one hour later.
65 mg/kg i.p.
65 mg/kg i.p., and with
The right hind limb of the recipient was
completely isolated from the body and was perfused at a fixed flow rate through the femoral artery with heparinized blood (37 C) from the carotid artery of a donor by the use of peri staltic pump (Mitsumi Science, SJ-1210). the end of the experiments.
The pump was precalibrated and re-checked at
The perfusion pressure was adjusted to about 100 mmHg at
the start of perfusion and maintained throughout the experiment.
The blood pressure of
the donor and the perfusion pressure were continuously measured by means of an individual
FIG. 1. Effects of methysergide on the sasoeonstrictor action of 5-HT, noradrenaline (Nor) and adenosine (Ads). A) Typical recordings. Note that the perfusion pressure (PP) remained unchanged after an injection of 0.3 ;,g of methysergide. Bl Summarized data. White (control) and oblique striated (treated) colums show the peak responses (mmHg) from the corresponding pre-drug levels to adenosine, noradrenaline and 5-HT before and after methysergide, respectively. Vertical bars represent means i SE (n 5). NS, not significant. The wet weights (H W) of the perfused right hind limb were ?4.5 0.6 (body weights of the recipient, 376.0_ 31.9 g) and the perfusion flow rate 11.1 x_0.8 ml/min/100 g HW. Initial perfusion pressure, 96.0-:_42 mmHg.
pressure transducer (Nihon Kohden, RP-5).
Recordings were made on an ink-writing
polyrecorder (TOA Electronics, EPR-3T). The venous outflow from the femoral vein of the isolated limb was received by a venous reservoir and in turn returned to the jugular vein of the donor by 15 cm drop of hydrostatic pressure.
Drug solutions were prepared
freshly with 0.9% saline before use and a volume of 0.01 ml was injected into the right femoral artery of the recipient over a 4 sec period.
As the perfusion rate was constant,
changes in the perfusion pressure caused by drugs were taken as drug responses. used were as follows:
)-noradrenaline
hydrochloride
The drugs
(Sankyo), 5-hydroxytryptamine
creatinine sulphate (5-HT, Sigma), adenosine (Wako Junyaku) and methysergide tartrate (Sandoz). Values in the text are means-~--SE. Student's t-test was used for statistical analyses and P values under 0.05 were considered significant. A single injection of either 5-HT (0.3 Pg) or noradrenaline (0.1 /eg) into the femoral artery had a constrictor effect on the vascular bed.
On the other hand, adenosine (10 ,ig)
induced a biphasic response, namely a marked and long-lasting constriction preceded by a brief vasodilatation.
Methysergide (0.3 / eg) which is a potent 5-HT antagonist (5), prevented
completely the vasoconstrictor effects of adenosine as well as of 5-HT, while it did not affect that of noradrenaline (Fig. IA and B). These results suggest that adenosine induces vasoconstriction either directly by acting on the tryptaminergic receptor or indirectly by releasing 5-HT from the stores. REFERENCES 1) BERNE,R.M.: Am. J. Physiol. 204, 317 (1963): 2) HASHIMOTO, K. ANDKuMAKLRA,S.: Japan. J. Physiol. 15, 540 (1965): 3) SATOH,S. ANDHASHIMOTO, K.: Tohoku J. exp. Mcd. 110, 367 (1973); 4) SAKAI,K., SUGANO, S., TAIRA,N. ANDHASHIMOTO, K.: Japan. J. Pharmacol. 24, 659 (1974); 5) DOUGLAS, W_W.: ThePharmacological Basis of Therapeutics,Edited by GOODMAN L.S. ANDGILMAN,A., p. 622, MacMillan Publishing Co., Inc., New York (1975)