|Budget Amount *help
¥4,000,000 (Direct Cost : ¥4,000,000)
Fiscal Year 1997 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1996 : ¥2,800,000 (Direct Cost : ¥2,800,000)
In this study supported by the Grant-in-Aid, we have aimed to clarify the mechanisms involved in rise of blood pressure and necrosis of the caput femoris due to heavy drinking.
Among impairments of health due to long-term heavy drinking, hepatopathy is well-known but almost no attention is paid to its renal effect and yet the kidney is deeply involved in fluctuations of the blood pressure and osteopathy.
We made systematic observations on ethanol administered rats making various experimental conditions by combining different days of starting the administration and the administrative periods. Through these observations, histologically we found that changes were recognized earlier in the kidney than in the liver and reported it in l987. Later on we also verified significant changes in the biochemical indices for renal functions.
In the present work we made the following studies ; (l) Measurement of both weak bound (Free, F) -and bound (B) -ethanol (Et) and acetaldehyde (AcAld) in the blood,
urine, and kidney of rats which discontinued drinking after long-term continual drinking. Observations on renal and hepatic tissues at the same time. (2) Measurement of F-and B-Et and AcAld in erythrocytes and urine of men who quit drinking after long-term heavey drinking. Observations on indices which are concerned with renal functions ; more concretely, these are renin, angiotensin I,angiotensin II,angiotenin converting enzyme (ACE), l alpha, 25 (OH)zD_3,24,25(OH)_2D_3 erythropoietin, etc. Observations on TG,UA,GOT,GPT,r-GTP,LPO,and CREN in connection with the hepatic function. Observations on ACE genotype and that of ALDH2 genotype.
After Et was administered to rats for 17 months and the administration was terminated, protein-bound Et and AcAld were found in the kidney in 48 and 96 hours. The histological findings : Antibody and
immune complex which were induced in response to protein-bound AcAld (antigen) where deposited as PAS positive deposits in glomerulus. Consequently, swelling of glomerulus, thickening of basement membrane of glomerulus, proliferation of mesangial cell, proliferation of juxtaglomerular cell, etc, which are generalized by the term "membranous nephropathy" were observed. Regarding the tubule, swelling and deciduation of tubular epithelial cell, hyaline droplet in tubular epithelial cell, cell infiltration to interstitial tissue, and basophilic tubule were observed.
In the course of the investigation of long-term heavy drinkers, amounts of F-AcAld and B-AcAld in erythrocytes were measured after the examinees stopped drinking for more than two months and the obtained values were two or three times as large as the values obtained from those who drink only small amount of alcohol. All indices, that is, renin, ACE,angiotensin I,II, 1alpha, 25(OH)_2D_3, and erythropoietin showed significantly high values in the long-term heavy drinkers group.
No specially clear changes were observed on indices for hepatic functions.
Through above observations, it is conceinable that the effect of long-term heavy drinking principally on the kidney is great and renin activities are high. The activities are especially high for those who have l/l type of ACE genotype and N/N type of ALDH2 genotype.
This leads to high value of angiotensin I and II,and brings a riseof the blood pressure. It is also concerned with contraction the blood vessels nourishing the epiphysis.
Fluctuations of 1alpha, 25(OH)_2D_3 are concerned with absorption of bone, e.g.osteoporosis.
We consider that we have had an important foundation of clarification of mechanisms of high blood pressure and bone impairment due to drinking. Less