scholarly journals Human Heme Oxygenase-1 Gene Transfer Lowers Blood Pressure and Promotes Growth in Spontaneously Hypertensive Rats

Hypertension ◽  
2001 ◽  
Vol 38 (2) ◽  
pp. 210-215 ◽  
Author(s):  
Hatem E. Sabaawy ◽  
Fan Zhang ◽  
Xuandai Nguyen ◽  
Abdelmonem ElHosseiny ◽  
Alberto Nasjletti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gene Transfer ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Functional Expression of Human Heme Oxygenase-1 Gene in Renal Structure of Spontaneously Hypertensive Rats

2003 ◽  
Vol 228 (5) ◽  
pp. 454-458 ◽  
Author(s):  
Alvin I. Goodman ◽  
Shou Quan ◽  
Liming Yang ◽  
Arika Synghal ◽  
Nader G. Abraham
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Rat Kidney ◽  
Functional Expression ◽  
Heme Oxygenase 1 ◽  
Thick Ascending Limb ◽  
Bile Pigments ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Heme oxygenase (HO), by catabolizing heme to bile pigments, regulates the levels and activity of cellular hemoprotein and HO activity. We examined the effect of delivery of the human HO-1 gene on cellular heme in renal tissue using a retroviral vector. We used a single intracardiac injection of the concentrated infectious viral particles in 5-day-old spontaneously hypertensive rats; 25 were transduced with empty vector and 25 were transduced with the human HO-1 gene. Functional expression of human and rat HO-1 was measured after 2 and 4 weeks. Reverse transcription polymerase chain reaction showed that human HO-1 mRNA was expressed as early as 2 weeks, with the highest levels in the kidney. Western blot analysis showed distribution of human HO-1 protein in rat kidney structures, predominantly in the thick ascending limb of the loop of Henle as well as in proximal tubules and preglomerular arterioles. These areas also demonstrated higher HO activity as measured by increased conversion of heme to bilirubin and carbon monoxide. Functional expression of the human HO-1 gene was associated with a decrease in blood pressure in 4- and 8-week-old spontaneously hypertensive rats. Compared with nontransduced rats, human HO-1 gene overexpression in transduced rats was associated with a 35% decrease in urinary 20-hydroxyeicosatetraenoic acid, a potent vasoconstrictor and an inhibitor of tubular Na+ transport, which may be related to the decrease in blood pressure.

Transfer of the Human Heme Oxygenase-1 Gene Decreases Blood Pressure and Promotes Growth in Spontaneously Hypertensive Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 730-730
Author(s):  
Hatem E Sabaawy ◽  
Fan Zhang ◽  
Alberto Nasjletti ◽  
Michal Laniado-Schwartzman ◽  
Nader G Abraham
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Body Weight Gain ◽  
Retroviral Vector ◽  
Left Ventricular ◽  
Intraluminal Pressure ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

P203 Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, free iron and carbon monoxide (CO). Both heme and CO have been implicated in the regulation of vascular tone. We report the successful cloning of the human HO-1 cDNA (HHO-1) into a LXSN retroviral vector (LSN-HHO-1). A single intra-left ventricular delivery of 1×10 10 pfu/ml of LSN-HHO-1 to 5-day-old spontaneously hypertensive rats (SHR; n = 32) resulted in extended expression of the human HO-1 (mRNA and protein) in several tissues, including the kidney, liver, spleen, lung, heart, brain and aorta. The expression of HHO-1 was associated with a 2-3 fold increase in HO activity in these tissues. Mean blood pressure (MBP) of SHR injected with LSN-HHO-1 was significantly lower than that of SHR injected with the control empty vector LXSN, by 4 weeks of age (144±4.6 mmHg vs 164.8±6.5 mmHg, n=32, * p <0.01). SHR treated with LSN-HHO-1 demonstrated a consistent reduction in MBP of ≈20 ± 4 mmHg when compared with the control LXSN injected SHR throughout the 20 weeks of the experiment. Administration of the HO inhibitor, stannic mesoporphyrin (Sn MP), to LSN-HHO-1-treated SHR resulted in a 15 to 18 mmHg rise of MBP, further suggesting that increased HO expression underlie, at least in part, the blood pressure lowering effect of LSN-HHO-1. Rats expressing HHO-1 showed significant reduction in the urinary excretion of the vasoconstrictor cytochrome P-450 arachidonate metabolite, 20-HETE. Moreover, gracilis muscle arterioles (≈ 55μm in diameter) isolated from HHO-1 transgenic SHR showed less contractile responses to increased intraluminal pressure than vessels isolated from LXSN-treated SHR; this effect was reversed by the addition of SnMP. Interestingly, HHO-1 transgenic rats showed significant proportionate increase in somatic growth, i.e., nose to tail length, fibula length and body weight gain. These studies demonstrate that delivery of the human HO-1 gene by a retroviral vector results in permanent expression of HHO-1, long-term reduction in blood pressure together with growth promoting activity in the SHR.

scholarly journals Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

2021 ◽  
Vol 22 (3) ◽  
pp. 1382
Author(s):  
Jelena Nesovic Ostojic ◽  
Milan Ivanov ◽  
Nevena Mihailovic-Stanojevic ◽  
Danijela Karanovic ◽  
Sanjin Kovacevic ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protein Expression ◽  
Hyperbaric Oxygen ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

scholarly journals Contribution of Heme Oxygenase 2 to Blood Pressure Regulation in Response to Swimming Exercise and Detraining in Spontaneously Hypertensive Rats

2018 ◽  
Vol 24 ◽  
pp. 5851-5859 ◽  
Author(s):  
Emine Kilic-Toprak ◽  
Ozgen Kilic-Erkek ◽  
Gulcin Abban-Mete ◽  
Vildan Caner ◽  
Ikbal Cansu Baris ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Blood Pressure Regulation ◽  
Swimming Exercise ◽  
Pressure Regulation ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

scholarly journals Hemin and L-arginine regulation of blood pressure in spontaneous hypertensive rats.

1991 ◽  
Vol 2 (6) ◽  
pp. 1078-1084 ◽  
Author(s):  
P Martasek ◽  
M L Schwartzman ◽  
A I Goodman ◽  
K B Solangi ◽  
R D Levere ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cytochrome P450 ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Dependent Manner ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity ◽  
Heme Arginate

Perturbation in heme metabolism is known to affect the level and activity of hemoproteins, including cytochrome P450-dependent arachidonic acid metabolism. The latter has been associated with elevation in blood pressure seen in spontaneously hypertensive rats. The effect of heme arginate and its components, arginine and heme, on cytochrome P450 levels and blood pressure in spontaneously hypertensive rats were studied. Administration of heme arginate or heme alone at doses of 9 to 30 mg/kg body wt/day for 4 days resulted in a marked decrease of blood pressure in spontaneously hypertensive rats, whereas blood pressure in rats receiving the vehicle control was not affected. Similarly, L-arginine, but not D-arginine, in a dose-dependent manner decreased blood pressure in spontaneously hypertensive rats. The maximal change in blood pressure was achieved at 100 mg/kg body wt of arginine and was associated with a significant increase in heme oxygenase activity. A higher concentration (500 mg/kg) did not cause an additional decrease in blood pressure but further increased heme oxygenase activity. The arginine-induced heme oxygenase activity was suppressed by Sn-protoporphyrin. Administration of heme to spontaneously hypertensive rats resulted in an accumulation of heme oxygenase mRNA, which was accompanied by an increase in enzyme activity. The increase in heme oxygenase activity was also prevented by Sn-protoporphyrin. It is postulated that heme treatment resulted in an increase in heme oxygenase mRNA, which consequently led to a diminution of cellular heme and depletion of hemoproteins, such as the cytochrome P450 arachidonate metabolizing enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

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