scholarly journals INDUCTION OF HEPATIC CYTOCHROME P450 ISOFORMS BY NICARDIPINE AT THERAPEUTIC DOSES IN SPONTANEOUSLY HYPERTENSIVE RATS

2007 ◽  
Vol 32 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Shoji MIYAJIMA ◽  
Kiyomitsu NEMOTO ◽  
Masashi SEKIMOTO ◽  
Yusuke KINAE ◽  
Toshihiko KASAHARA ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Cytochrome P450 Isoforms ◽  
Therapeutic Doses ◽  
Hepatic Cytochrome

Abstract 181: Overexpression of Arachidonic Acid Cytochrome P450 Expoxygenases Prevents the Development of High Blood Pressure via Enhancing Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dao Wen Wang ◽  
Bin Xiao ◽  
Yong Wang ◽  
Xiaojun Xiong ◽  
Darryl C Zeldin
Keyword(s):  
Blood Pressure ◽  
Cytochrome P450 ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Spontaneously Hypertensive Rats ◽  
Hypotensive Effect ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Atrial Natriuretic

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have potent vasodilatory and diuretic feature, and therefore potentially hypotensive effect. No in vivo studies, however, were performed to support it. This study investigated the hypothesis via overexpressing CYP epoxygense genes in spontaneously hypertensive rats (SHR). Recombinant adeno-associated virus vector (rAAV) was utilized to mediate long-term transfection of CYP2J2 and CYP2C11 genes, respectively, in adult SHR, and animal systolic blood pressure (SBP) was monitored using arterial caudilis indirect manometric method. Results showed that at 2 months the urinary excretion of stable hydrolysis metabolic product of 14, 15-EE, 14–15-DHET increased by 11 and 8.7 folds in rAAV-2J2 and rAAV-2C11 groups, respectively, compared with AAV-GFP-treated rats. (2) SBP in 2J2- and 2C11-treated rats decreased from 175.0 ± 2.8mHg to 163.5 ± 5.8mmHg and 161.2 ± 6.1 mmHg, respectively, ( p <0.01) at month 2, and it is 165.0 ± 4.7 mmHg and 173.0 ± 12.8 mmHg at month 6 after gene injection (~30mmHg and ~23mmHg lowerer than that in control animals, respectively, p <0.001). (3) Before the rats were sacrificed, cardiac function tests with Pressure-Volume System showed that maximum intracardiac pressure was 202.1 ± 30.0 & 209.1 ± 17.1mmHg in two gene-treated rats, respectively, significantly lower than control (241.2 ± 18.2mmHg, p <0.01) and cardiac output in treatment rats were significantly higher than control (p<0.05). (4) Interestingly, atrial natriuretic peptide (ANP) mRNA were up-regulated 6–14 folds respectively in myocardium of 2J2 and 2C11 groups; furthermore, C-type receptor mRNA of ANP was increased in heart, lung, kidney and aorta. (5) in cultured atrial cells (HLB2G5), exogenous EETs stimulated ANP production. In conclusions, for first time our data indicates overexpression of CYP2J2 or CYP2C11 could prevent development of hypertension in SHR, improve cardiac functions, which may involve up-regulating ANP expression and its receptors in target tissues, which suppresses collagen deposition and cardiovascular remodeling.

Expression and Inducibility of Cytochrome P450 Iiia Family within Intrasplenically Transplanted Fetal Hepatocytes

1996 ◽  
Vol 5 (1) ◽  
pp. 117-122 ◽  
Author(s):  
Kazuya Kato ◽  
W. John B. Hodgson ◽  
Nader G. Abraham ◽  
Kazhuiko Onodera ◽  
Masato Imai ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Microscopic Examination ◽  
Spontaneously Hypertensive Rats ◽  
Hepatocyte Proliferation ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Immunohistochemical Stain ◽  
Fetal Hepatocytes ◽  
Red Pulp

With the development of transplantation of hepatocytes into the spleen, interest has focused on the metabolic changes associated with hepatocyte proliferation. As these changes are important for drug metabolism in hepatocytes, we examined the expression and inducibility of the cytochrome P450 IIIA family within transplanted hepatocytes. Fetal hepatocytes were harvested at 20 days of gestation from spontaneously hypertensive rats (SHRs) and transplanted into recipient adult SHR spleens. Microscopic examination of the recipient spleens 4 and 10 wk after transplantation revealed masses of hepatocytes with cordlike structures in the red pulp. Proliferating hepatocytes were detected with a bromodeoxyuridine (BrdU) immunohistochemical stain. Immunochemical studies detected cytochromes (cytos) P450 p and P450 HLp in fetal hepatocytes before transplantation without prior induction. And although these cytos were not detected by 10 wk after transplantation, they were induced with dexamethasone. These results demonstrated that fetal hepatocytes can be transplanted successfully into recipient spleens and suggested that fetal hepatocytes grow in the spleen, similar to the adult hepatocyte response.

Regulation of 11?? -hydroxylase cytochrome P450 expression by cholesterol in spontaneously hypertensive rats

1995 ◽  
Vol 13 (11) ◽  
pp. 1253-1258 ◽  
Author(s):  
Speranza Rubattu ◽  
Rosaria Russo ◽  
Bruna Gigante ◽  
Antonio Porcellinit ◽  
Luciana Finizia ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
P450 Expression

Enzymatic Activity and Expression of Cytochrome P450 LAω within Intrasplenically Transplanted Fetal Hepatocytes in Spontaneously Hypertensive Rats

1997 ◽  
Vol 6 (5) ◽  
pp. 531-534 ◽  
Author(s):  
Kazuya Kato ◽  
Junji Kato ◽  
W. John B. Hodgson ◽  
Nader G. Abraham ◽  
Kazuhiko Onodera ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Enzymatic Activity ◽  
Microscopic Examination ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Hydroxylase Activity ◽  
Spontaneously Hypertensive ◽  
Fetal Hepatocytes ◽  
Red Pulp

We examined the expression and enzymatic activity of the cytochrome P450 LAω within transplanted hepatocytes. Fetal hepatocytes were harvested at day 20 of gestation from spontaneously hypertensive rats (SHRs) and transplanted into recipient adult SHR spleens. Microscopic examination of the recipient spleens 4 and 10 wk after transplantation revealed masses of hepatocytes with cordlike structures in the red pulp. Immunochemical studies detected cytochrome (cyto) P450 LAω in the fetal hepatocytes before transplantation without prior induction. Although the cyto P450 LAω was not detected by the second week after transplantation, by the 6th and 10th wk after transplantation, it was. Cyto P450-arachidonic acid ω/4oM-1 hydroxylase activity (formation of 20- and 19-hydroxyeico-satetraenoic acid) was detected at 10 wk after transplantation, but not 2 or 6 wk after transplantation. These results demonstrated that fetal hepatocytes can be transplanted successfully into recipient spleens and then grow in the spleens, as in the case of the adult hepatocyte response.

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