견성고혈압과 catecholamine과의 관계

Abstract

[한글]

The Relationship of Renal Hypertension and Catecholamines

Choi, Ha Kyung

Department of Pharmacology Yonsei University College of Medicine, Seoul, Korea

(Directed Prof. Woo CHoo Lee)

It is well established that renin, a proteoclytic enzyme, is produced by the

ischaemic and acts on a plasma globulin fraction known as hypertensinogen,

resulting in formation of gypertensin or angiotonin which causes hypertension. By

using various methods for testing the response to injected catecholamines in renal

hypertensive animals, sensitivity was found to be either increased or decreased. An

increase in the pressor response to the injection of sympathomimetic amines has

been claimed in human hypertension. Furthermore, Bing(1946) reported that renal

ischaemia caused a diminution of the activity of amine oxidase and thus brought

about and accumulation of pressor amines in the blood. Recently, Champlain et

al.(1966) have shown a reduction in the accumulation of H**3-norepinephrine in the

experimental hypertension.

The present experiments were undertaken to examine whether catecholamine splay

any role in the production of renal hypertension.

Experiments were conducted on adult albino rabbits of both sexes. Renal

hypertension was produced by placing figure-of-eight ligature around each pole in

the right kidney, leaving the renal pedicle intact. In some experiments, the

contralateral renal artery was constricted about a week after the ligature of the

right kidney. Blood pressure was measured at an interval of 3 days by ear capsule

technique of Grant and Rothschield(1934). However, at the end of 3 weeks after the

ligature of the right kidney, the carotid arterial blood pressure was directly

determined by mercury manometer and the rabbits were killed for further

experiments.

The isolated atria and aortic strips were prepared according to the procedures

described by Lee and Shideman(1959) and Furchgott(1960) respectively. The tissue

catecholamines were determined spectrophotofluorometrically by the method of Shore

and Olin(1958). At the same time, tissues were fixed in 10% formalin. Microsections

were prepared after paraffin embedding and stained with hematoxylin and eosin.

RESULTS

1. In the rabbits the application of a figure-of-eight ligature on the unilateral

kidney resulted in a significant elevation of the blood pressure within few days

and this hypertension was maintained during the course of three weeks of the

experiment.

2. At the end of three weeks of renal hypertension, there was no changes in the

weight of the heart but a significant increase in the weight of adrenal glands.

Histological examination revealed a marked hypertrophy of the zona glomeruloss. A

compensatory hypertrophy of the left kidney was also observed after the ligature of

the right kidney.

3. During the three weeks of renal hypertension, the catecholamine content was

markedly increased in the heart, whereas it was decreased in the kidney. However,

no significant changes were observed in the adrenal catecholamines during the renal

hypertension.

4. The pressor response to the injection of standard dose of epinephrine was

markedly enhanced in rabbits which were rendered hypertensive by renal ischaemia.

5. The cardiostimulant action of norepinephrine was more marked in the isolated

atria from renal hypertensive rabbits compared to those from normal animals.

6. The vasoconstrictor activity of norepinephrine was also more marked in the

isolated aortic strips from renal hypertensive rabbits than those from normotensive

control rabbits.

7. Hexamethonium, dibenzyline and reserpine lowered the blood pressure of the

renal hypertensive rabbits but the hypotensive activities of these drugs were not

greater than those observed in the normal rabbits.

[영문]

It is well established that renin, a proteoclytic enzyme, is produced by the ischaemic and acts on a plasma globulin fraction known as hypertensinogen, resulting in formation of gypertensin or angiotonin which causes hypertension. By using various methods for testing the response to injected catecholamines in renal

hypertensive animals, sensitivity was found to be either increased or decreased. An increase in the pressor response to the injection of sympathomimetic amines has been claimed in human hypertension. Furthermore, Bing(1946) reported that renal ischaemia caused a diminution of the activity of amine oxidase and thus brought about and accumulation of pressor amines in the blood. Recently, Champlain et al.(1966) have shown a reduction in the accumulation of H**3-norepinephrine in the experimental hypertension.

The present experiments were undertaken to examine whether catecholamine splay any role in the production of renal hypertension.

Experiments were conducted on adult albino rabbits of both sexes. Renal hypertension was produced by placing figure-of-eight ligature around each pole in the right kidney, leaving the renal pedicle intact. In some experiments, the contralateral renal artery was constricted about a week after the ligature of the

right kidney. Blood pressure was measured at an interval of 3 days by ear capsule technique of Grant and Rothschield(1934). However, at the end of 3 weeks after the ligature of the right kidney, the carotid arterial blood pressure was directly

determined by mercury manometer and the rabbits were killed for further experiments.

The isolated atria and aortic strips were prepared according to the procedures described by Lee and Shideman(1959) and Furchgott(1960) respectively. The tissue catecholamines were determined spectrophotofluorometrically by the method of Shore

and Olin(1958). At the same time, tissues were fixed in 10% formalin. Microsections were prepared after paraffin embedding and stained with hematoxylin and eosin.

RESULTS

1. In the rabbits the application of a figure-of-eight ligature on the unilateral kidney resulted in a significant elevation of the blood pressure within few days and this hypertension was maintained during the course of three weeks of the experiment.

2. At the end of three weeks of renal hypertension, there was no changes in the weight of the heart but a significant increase in the weight of adrenal glands.

Histological examination revealed a marked hypertrophy of the zona glomeruloss. A compensatory hypertrophy of the left kidney was also observed after the ligature of the right kidney.

3. During the three weeks of renal hypertension, the catecholamine content was markedly increased in the heart, whereas it was decreased in the kidney. However, no significant changes were observed in the adrenal catecholamines during the renal hypertension.

4. The pressor response to the injection of standard dose of epinephrine was markedly enhanced in rabbits which were rendered hypertensive by renal ischaemia.

5. The cardiostimulant action of norepinephrine was more marked in the isolated atria from renal hypertensive rabbits compared to those from normal animals.

6. The vasoconstrictor activity of norepinephrine was also more marked in the isolated aortic strips from renal hypertensive rabbits than those from normotensive control rabbits.

7. Hexamethonium, dibenzyline and reserpine lowered the blood pressure of the renal hypertensive rabbits but the hypotensive activities of these drugs were not greater than those observed in the normal rabbits.