Adenosine tetraphosphate가 쥐의 심혈관계에 미치는 영향

Abstract

[영문]

[한글]

세포내에서 여러 가지 능동적 과정의 1차적인 에너지 원으로 이용되는 nucleotides는

비록 적은 양이기는 하하 세포외액에소 존재하며 주로 혈관저항 및 조직 대사에 영향을

미치는 것으로 알려졌다. Adenine nucleotides는 신동맥을 비롯한 일부의 혈관을 수축시

키기도 하나 일반적으로 대부분의 혈관계에서 혈관이완을 나타낸다. 이와같은 nucleotide

s의 혈관수축 및 이완반응은 혈관의 부위에 따라 상이할뿐만 아니라 동물의 종, nucleoti

des의 농도 및 평활근의 수축정도에 따라 다르게 나타난다.

근자에는 ATP(Adenosine triphosphate) 혹은 adenosine을 신경전달 물질로 사용하는 퓨

린성 신경계의 존재가 알려졌다. 퓨린성 수용체는 여러 가지 세포에 존재하며 약리학적

및 기능적 기준에 의해 P^^1 수용체와 P^^2 수용체로 구분되고 심장 및 혈관에서도 그 존

재가 확인되었다. 그러나 이들 수용체가 활성화 된 후 어떤 기전을 통해 효과를 나타내는

지는 아직 확실치 않다.

본 연구에서는 ATPP(adenosine tetraphosphate)가 쥐의 혈압, 심박동수 및 심근수축력

에 미치는 영향을 관찰하고 ATP와의 효과를 비교해 봄으로써 심장 및 혈관에 존재하는 퓨

린성 수용체의 성질중 일부를 밝히고자 하였다. 200-300gm의 흰쥐를 Na-thiopental(300mg

/Kg)로 마취하고 기관절개를 시행하여 기도를 확보하였다. 좌측 경동맥을 통해 대동맥 궁

내로 ATPP 및 ATP를 부여하고 대퇴동맥에서 혈압 및 심박동수를 측정하여 physiograph(Na

rco, MK-III)에 기록하였다. 실험에 따라서는 우측대퇴동맥을 통해 실혈시켜 저혈압 상태

가 되게한 후 ATP 및 ATP를 투여하고 정상혈압 상태에서의 효과와 비교하였다. In vitro

실험에서는 심장을 적출하여 좌, 우 심방을 각각 분리하였고 전기장 자극하의 좌심방으로

부터는 심근수축력을, 우심방으로 부터는 심박동수를 측정하였으며 (Grass, 7E) ATPP 및

ATPP 투여시 효과를 관찰하였다. 이때 incubation 용액으로는 Krebs-Ringer bicarbonate

를 사용하였으며 실험기간동안 95% O^^2/5% CO^^2를 공급하여 pH가 7.4되게 하였다.

중요 실험결과는 아래와 같다.

1. ATPP 투여시 적은 양(10, 20, 100 nmoles)에서는 혈압을 감소시켰고 많은 양 (200,

400 nmoles)에서는 혈압을 상승시켰다.

2. 100 nmoles의 ATPP를 투여 했을 때 정상혈압상태에서는 혈압 감소를, 저혈압 상태에

서는 혈압상승을 나타냈다.

3. ATP의 경우 정상혈압 상태일때나 저혈압 상태일 때 정도의 차이는 있으나 모두 혈압

을 감소시켰다.

4. 분리된 심방근에서 ATPP는 심근 수축력 및 심박동수를 효과적으로 감소시켰다.

이상의 성적으로 보아 ATPP는 혈관계에 존재하는 퓨린성 수용체에 작용하여 혈관의 이

완 및 수축에 관여하고 일부는 ATP와 다른 기전으로 혈관운동에 관여 하리라 생각된다.

Effects of Adenosine Tetraphophate on the Rat Cardiovascular System

In Deok Kong

Department of Medical Science The Graduate School, Yonsei University

(Directed by Associate Professor Joong Woo Lee, Ph.D.)

Adenosin 5'-triphosphate(ATP) was primarily regarded as an intracellular energy

source for most active processes in a cell.

However, a small quantity of extracellular ATP have been known to have an effects

upon the vascular resistance and metaboli는 in various tissues.

Adenosin mucleotides are chiefly potent vasodilators in various vascular beds

although they serve as a vasoconstrictors in a few vascular beds including renal

artery complex. The contrary actions of adenine nucleotides have been found to be

dependent on the site of vascular, animal species, concentration of drug and basal

tone of smooth muscle, etc.

Recently, the purinergic nervous system, which releases purine nucleotide, ATP as

principal neurotransmitter, was recognized.

Purinergic receptors have also been identified in various tissues and cell types

and classified as P^^1-and P^^2-purinoceptors according to their functional and

pharmacological criteria. But the mechanism producing a responce after activation

of the purinoceptor is still uncertain.

In this study, attempts were made to investigate following:

1. The effects of adenosin tetraphosphate(ATPP) on the cardiovascular system of

the rat - blood pressure, heart rate and cardiac contractility in comparison with

ATP in particular.

2. Some characteristics of purinoceptors in the heart and systemic vasculature.

Sprague-Dawely rats (200-300 gm) were anesthetized with Na-thiopental (30 mg/Kg).

The free airway was ensured by tracheostomy to allow the animals to breathe

spontaneously. The left femoral artery was cannulated with a polyethylene tube

placed in the retrograde direction for recording blood pressure and heart rate.

Adenosin nucleotides(ATPP, ATP) were administered systemically via a cannula

inserted in the left carotid artery with its tip in the opening of the aortic arch.

Blood pressure and heart rate were monitored by means of a pressure transducer

and a biotachometer in the course of the experiment and then recorded on a

physiograph(Narco, MK-III). In some experiments the hypotensive state was induced

by hemorrhage via a cannula inserted in the right femoral artery to compare the

effects of these drugs induced in the normotensive state.

In the in vitro experiments, the rat was stunned by a head blow. The right and

left atria of the heart were isolated immediately and transferred to an organ bath.

One side of the atrium was fixed to the bottom of the bath and the other to a force

transducer(FT03C). The cardiac contractility of the left atrium, which was under

electrical field stimulation, and the heart rate of the right atrium with intact SA

node, were recorded respectively on the polygraph(Grass, 7E). After equilibrium for

30 min. adenine nucleotides were added to the incubation medium. The incubation

medium was a Krebs-Ringer bicarbonate solution, into which 95% O^^2/5% CO^^2 gas

was bubbled, giving a pH of 7.4.

The main results of the experiments were as follows:

1. Blood pressure was decreased by the administration of ATPP in small

quantities(10, 20 and 100 nmoles) but increased by large (200 & 400 nmoles)

quantities.

2. ATPP decreased blood pressure in the normotensive state but rather increased

it in the hypotensive state when 100 nmoles of the drug was administered.

3. ATP decreased blood pressure in both the normotensive and hypotensive states

although there was a difference in degree of change.

4. ATPP decreased contractility and heart rate effectively in the isolated

atrium.

In conclusion, ATPP may act on purinoceptors in the cardiovascular system to

induce vasodilation and/or vasoconstriction and the action mechanisms of ATPP may

be different from those of ATP.