Effect of Calcium Channel Blocker on Gene Expression of Renin after lschemic Renal Injury.
- Author:
Kyu Beck LEE
;
Dae Ryong CHA
;
Yong Seop KIM
;
Won Yong CHO
;
Hyoung Kyu KIM
- Publication Type:Original Article
- Keywords:
Renin;
gene expression;
Calcium hannel blocker;
Ischemic renal injury
- MeSH:
Adenosine Triphosphate;
Angiotensins;
Animals;
Calcium Channel Blockers;
Calcium Channels*;
Calcium*;
Cell Membrane;
Constriction;
Electrophoresis;
Formaldehyde;
Gene Expression*;
Humans;
Ischemia;
Kidney;
Membranes;
Nephrectomy;
Nifedipine;
Rats;
Rats, Sprague-Dawley;
Regeneration;
Renal Artery;
Renal Circulation;
Renin*;
Renin-Angiotensin System;
Reperfusion;
RNA;
Sepharose
- From:Korean Journal of Medicine
1997;53(3):325-333
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVES: lschemic acute renal failure(ARF) is characterized by an abrupt and sustained decline in GFR within minutes to days after renal ischemia and not immediately reversed on restoration of renal blood flow. The typical delay of a few days to a few weeks suggests reversible parenchymal damage awaiting cell regeneration for functional recovery. Many potentially cell damaging factors, such as ATP depletion, plasma membrane phospholipid degradatian and superoxide-induced membrane damage, play a central part in ischemic injury. More recently, much attention has been focused on the role of calcium, especially ischemic cell injury and the possible therapeutic role of calcium channel blockers emerged from studies conducted several years ago. In the past, it was thought that activation of renin-angiotensin system plays a role in the pathogenesis of ARF. Now the role of angiotensin in human renal ischemia also appears to be controversial. The following study was done in order to investigate the effect of a calcium channel blocker, nifedipine, on gene expression of renin during acute ischemic renal injury. METHODS: The Sprague-Dawley rats were divided into 4 groups, group I(n=3) as the control, group II (n=3) as the sham operation group, group III(n=15) as the ischemic renal injury group without nifedipine pretreatment, and group IV(n=15) as the ischemic renal injury model by right nephrectomy and left renal artery clamping for 40 minutes with systemic nifedipine pretreatment(10mg/kg), 1n ischemic renal injury model(group III and IV), rats were further divided into three subgroups according to reperfusion time of 1,24,72 hours. The non-ischemic right kidney removed at the time of initial procedure served as paired control. Total renal RNA was extracted by Chomczynskis method and electrophoresis was done in a 1% agarose gel containing 2,2M formaldehyde. Northern was performed at 42degrees C with isotope labeled renin probe for 18 hours, Autoradiographs were obtained and quantitated by a densitometer measured at 530nm. RESULTS: 1) The expression of renin gene was markedly decreased after renal ischemia and slowly recovered to one half of the control level after 72 hours of reperfusion. 2) Renin gene expression pattern of ischemic renal injury with prior nifedipine treatment was similar to the ischemic group without nifedipine pretreatment. CONCLUSION: These findings suggest that the renin gene expression was markedly decreased after renal ischemia and slowly recovered. Systemic nifedipine pretreatment does not have a significant effect on gene expression pattern of renin in ischemic renal injury.
