scholarly journals 20-HETE and CYP4A2 ω-hydroxylase contribute to the elevated blood pressure in hyperandrogenemic female rats

2016 ◽  
Vol 311 (1) ◽  
pp. F71-F77 ◽  
Author(s):  
Carolina Dalmasso ◽  
Rodrigo Maranon ◽  
Chetan Patil ◽  
Mohadetheh Moulana ◽  
Damian G. Romero ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Hydroxylase Activity ◽  
Sprague Dawley Rats ◽  
Low Salt ◽  
Cytochrome P 450

In male rats, androgen supplements increase 20-hydroxyeicosatetraenoic acid (20-HETE) via cytochrome P-450 (CYP)4A ω-hydroxylase and cause an increase in blood pressure (BP). In the present study, we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague-Dawley rats (96 ± 2 vs. 108 ± 2 mmHg, P < 0.05) and was associated with increased renal microvascular CYP4A2 mRNA expression (15-fold), endogenous renal 20-HETE (5-fold), and ω-hydroxylase activity (3-fold). Chronic DHT also increased MAP in low salt-fed Dahl salt-resistant female rats (81 ± 4 vs. 95 ± 1 mmHg, P < 0.05) but had no effect on MAP in Dahl salt-sensitive female rats (154 ± 3 vs. 153 ± 3 mmHg), which are known to be 20-HETE deficient. To test the role of CYP4A2, female CYP4A2−/− and SS.5Bn (wild type) rats were treated with DHT. DHT increased MAP in SS.5Bn female rats (104 ± 1 vs. 128 ± 1 mmHg, P < 0.05) but had no effect in CYP4A2−/− female rats (118 ± 1 vs. 120 ± 1 mmHg). Renal microvascular 20-HETE was reduced in control CYP4A2−/− female rats and was increased with DHT in SS.5Bn female rats (6-fold) but not CYP4A2−/− female rats. ω-Hydroxylase activity was 40% lower in control CYP4A2−/− female rats than in SS.5Bn female rats, and DHT decreased ω-hydroxylase activity in SS.5Bn female rats (by 50%) but significantly increased ω-hydroxylase activity in CYP4A2−/− female rats (3-fold). These data suggest that 20-HETE via CYP4A2 contributes to the elevation in BP in hyperandrogenemic female rats. The data also suggest that 20-HETE synthesis inhibition may be effective in treating the elevated BP in women with hyperandrogenemia, such as women with polycystic ovary syndrome.

scholarly journals Kidney dopamine D1-like receptors and angiotensin 1–7 interaction inhibits renal Na+ transporters

2019 ◽  
Vol 317 (4) ◽  
pp. F949-F956 ◽  
Author(s):  
Anees A. Banday ◽  
Andrea Diaz Diaz ◽  
Mustafa Lokhandwala
Keyword(s):  
Blood Pressure ◽  
Tyrosine Hydroxylase ◽  
Cumulative Effect ◽  
Sprague Dawley ◽  
Hydroxylase Activity ◽  
Tyrosine Hydroxylase Activity ◽  
Sprague Dawley Rats ◽  
Renal Dopamine ◽  
G Protein Coupled

The role of dopamine D1-like receptors (DR) in the regulation of renal Na+ transporters, natriuresis, and blood pressure is well established. However, the involvement of the angiotensin 1–7 (ANG 1−7)-Mas receptor in the regulation of Na+ balance and blood pressure is not clear. The present study aimed to investigate the hypothesis that ANG 1–7 can regulate Na+ homeostasis by modulating the renal dopamine system. Sprague-Dawley rats were infused with saline alone (vehicle) or saline with ANG 1–7, ANG 1–7 antagonist A-779, DR agonist SKF38393, and antagonist SCH23390. Infusion of ANG 1–7 caused significant natriuresis and diuresis compared with saline alone. Both natriuresis and diuresis were blocked by A-779 and SCH23390. SKF38393 caused a significant, SCH23390-sensitive natriuresis and diuresis, and A-779 had no effect on the SKF38393 response. Concomitant infusion of ANG 1–7 and SKF38393 did not show a cumulative effect compared with either agonist alone. Treatment of renal proximal tubules with ANG 1–7 or SKF38393 caused a significant decrease in Na+-K+-ATPase and Na+/H+ exchanger isoform 3 activity. While SCH23390 blocked both ANG 1–7- and SKF38393-induced inhibition, the DR response was not sensitive to A-779. Additionally, ANG 1–7 activated PKG, enhanced tyrosine hydroxylase activity via Ser40 phosphorylation, and increased renal dopamine production. These data suggest that ANG 1–7, via PKG, enhances tyrosine hydroxylase activity, which increases renal dopamine production and activation of DR and subsequent natriuresis. This study provides evidence for a unidirectional functional interaction between two G protein-coupled receptors to regulate renal Na+ transporters and induce natriuresis.

Abstract P040: Role of 20-HETE in Elevated Blood Pressure in Hyperandrogenemic Female Rats, a Model of Polycystic Ovarian Syndrome

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Chetan N Patil ◽  
Carolina Dalmasso ◽  
Rodrigo O Maranon ◽  
Huimin Zhang ◽  
Richard J Roman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Polycystic Ovary ◽  
Premenopausal Women ◽  
Female Rats ◽  
Elevated Blood Pressure ◽  
Female Rat ◽  
Elevated Blood ◽  
Reproductive Disorder ◽  
Consomic Strain

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in premenopausal women, is characterized by hyperandrogenemia, metabolic syndrome and inflammation. They also exhibit elevated blood pressure (BP) but may not be treated since they do not meet the criteria for hypertension (BP>130/90 mm Hg). We have characterized a female rat model of hyperandrogenemia (HAF) using dihydrotestosterone (DHT) that mimics many characteristics of women with PCOS. In the present study we tested the hypothesis that androgen-induced upregulation of the cytochrome P450 4A2 isoform (CYP4A2) and the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) in renal microvasculature contributes to the elevated BP in HAF rats. Female rats of SS.5BN consomic strain (wild type) rats and CYP4A2-/- rats on this same background were implanted with DHT (7.5mg/90d) or placebo pellets (n=5-8/grp) beginning at 6 wks of age; pellets were changed every 85 d. At 14 wks of age, rats were implanted with radiotelemetry transmitters, and mean arterial pressure (MAP) was measured for 10 days. Endogenous 20-HETE levels were measured using LC-MS in renal microvessels isolated using an Evans Blue sieving technique. DHT-treated HAF-SS.5BN rats had significantly higher MAP compared to placebo-SS.5BN (128±6 vs. 104±1 mmHg, p<0.004). In contrast, HAF-CYP4A2-/- rats had no change in MAP compared to placebo-CYP4A2-/- controls (120±4 vs 118±3 mmHg, p=NS). Endogenous 20-HETE levels in renal microvessels of HAF-SS.5BN rats were significantly increased compared to Placebo-SS.5BN (2.27±0.91 vs. 0.32±0.037 pmol/mg, p<0.01). The 20-HETE levels were lower in CYP4A2-/- than SS.5BN but DHT in HAF-CYP4A2-/- had no effect on 20-HETE levels compared to Placebo- CYP4A2-/-. These results suggest that androgen-mediated upregulation of the expression of CYP4A2 and the production of 20-HETE in renal microvessels contribute to elevated BP in HAF rats. These data also suggest that methods to attenuate 20-HETE may provide a novel therapeutic to reduce BP in women with PCOS. Work supported by NIH RO1HL66072 and PO1HL51971.

Abstract P045: Sex And Age Specific Circulating Aldosterone Changes In Transgenic Hypertensive (mRen2)27 Rats And Hannover Sprague Dawley (SD) Rats And Its Association With Blood Pressure And Cardiac Function

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Fatima Ryalat ◽  
N Cruz-Diaz ◽  
W Graham ◽  
T Gwathmey-Williams ◽  
P E Gallagher ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Cardiac Function ◽  
Target Organ Damage ◽  
Aging Effect ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Aldosterone Antagonists ◽  
Sd Rats

Aldosterone plays a significant role in hypertension and target organ damage. Aldosterone antagonists are used in the management of heart failure. However, neither the influence of age nor sex on aldosterone pathophysiology is well understood. We investigated the changes in circulating aldosterone with age and its association with cardiovascular function, using male and female hypertensive renin transgenic (mRen2)27 rats and SD rats at 20 and 50 weeks of age. Both male (22 ± 3 vs. 12 ± 2 ng/dL, n = 9 - 12, p < 0.05) and female (59 ± 10 vs. 23 ± 8 ng/dL, n = 6 - 10, p < 0.05) hypertensive rats had higher serum aldosterone compared with SD rats at 20 weeks of age. At 50 weeks of age, the difference persisted in the hypertensive female rats (63 ± 8 vs. SD: 33 ± 7 ng/dL, n = 6 - 7, p < 0.05), but not in the males. SD male rats have higher systolic blood pressure (SBP) as they age, and consequently develop cardiac diastolic dysfunction associated with higher aldosterone at 50 weeks compared to 20 weeks (28 ± 3 vs. 12 ± 2 ng/dL, n = 7 - 9, p < 0.05). This aging effect on aldosterone was not significant in the other groups. We showed previously that SD males treated with polyphenol rich muscadine grape extract (MGE) have lower aldosterone, less aortic stiffness and better cardiac diastolic function (E/e’) than controls at the older age; the MGE effect was not seen in (mRen2)27 males. Sex differences in aldosterone were not significant in the SD rats at either time point. However, (mRen2)27 female rats had higher aldosterone than (mRen2)27 males at both 20 weeks (59 ± 10 vs. 22 ± 3 ng/dL, n = 10 - 12, p < 0.05) and 50 weeks (63 ± 8 vs. 31 ± 7 ng/dL, n = 6 - 7, p < 0.05), despite the lack of significant differences in SBP. (mRen2)27 female rats preserve cardiac function better than males throughout their life span, while males develop indices of heart failure. Our data suggest that lower aldosterone levels in hypertensive males compared with females do not protect against the higher lifetime burden of elevated SBP and also may reflect different mechanisms controlling circulating aldosterone between sexes. In addition, data suggest a potential therapeutic effect of MGE in the management of age-associated moderate hypertension.

Sexual dimorphism in vasopressin-induced contraction of rat aorta

1991 ◽  
Vol 260 (2) ◽  
pp. H453-H458 ◽  
Author(s):  
J. N. Stallone ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Estrous Cycle ◽  
Vascular Reactivity ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Female Rats ◽  
Male Rats ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Tension Development ◽  
Sprague Dawley Rats

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Effect of a Mediterranean Meal on Sprague Dawley Rats DMBA-Induced Mammary Tumors

2010 ◽  
Vol 3 ◽  
pp. CGM.S5894
Author(s):  
Paula C. Pereira ◽  
A. Filipa Vicente ◽  
Maria F. Mesquita ◽  
Antonio S. Cabrita
Keyword(s):  
Experimental Studies ◽  
Protective Role ◽  
Female Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Total Cancer ◽  
Group A ◽  
Histopathologic Analysis ◽  
Group B

The present study intents to find a possible protective role of a Mediterranean type meal on mammary carcinogenesis. Several factors have been associated with breast cancer risk, genetics and environment are the most pointed out in epidemiologic and experimental studies. Diet is an environmental factor that can promote or prevent disease, being responsible for almost 35% of total cancer cases. A total of 72 female rats 50 days old were randomly divided in three groups of 24 rats and housed 4 in each plastic cage in a holding room under constant conditions of 22 ± 2 °C, 55 ± 10% humidity and a 12 h light/dark cycle. All the animals were submitted to the administration of 20 mg of 7, 12 dimethylbenzanthracene (DMBA) in olive oil, by gavages, except group A. The same defined standard food was provided for all the animals in group A and B, supplemented with a Mediterranean meal in group C. All the animals were sacrificed by the end of 150 days. Total carcinoma number did not differ significantly between Groups B and C and there were not found any neoplastic lesions in Group A. Most tumors showed a mixed architectural pattern, with cribriform and papillary areas, comedocarcinoma and necrosis was only seen in Group B. Histopathologic analysis showed that Group C tumors had lower mitotic activity and Pattern Grades, but higher Nuclear Grades. Mediterranean diet type meal showed lower Pattern Grades and lower Mitotic count in spite of that a higher nuclear pleomorphism was also found. Even so, tumors from Group C were better differentiated which can indicate lower malignancy.

scholarly journals Some nutritional properties of unrefined sugar and its promotion of the survival of new-born rats

1985 ◽  
Vol 54 (3) ◽  
pp. 593-603 ◽  
Author(s):  
Eisa Omer Ahmed ◽  
Yudkin John
Keyword(s):  
Fatty Acid Synthetase ◽  
Female Rats ◽  
Male Rats ◽  
Blood Cholesterol ◽  
Maize Starch ◽  
Sprague Dawley ◽  
Brown Sugar ◽  
Sprague Dawley Rats ◽  
Male Wistar Rats ◽  
Glucose 6 Phosphate Dehydrogenase

1. The claims that rats fed on diets with ‘brown sugar’ (unrefined muscovado) perform better in a number of ways than do rats fed on refined white sugar (sucrose) have been examined.2. Male Wistar rats were fed on purified diets from weaning, in which the carbohydrate component was either maize starch or unrefined sugar or sucrose. The sugars produced no differences in growth rate, body composition, or the weights of liver or kidneys. Compared with sucrose, unrefined sugar produced an increase in blood cholesterol and in the activity of hepatic fatty acid synthetase, and a greater increase in blood triglyceride. In confirmation of earlier results, rats fed on either sugar had heavier livers and kidneys, increased activity of hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and a higher concentration of plasma triglyceride compared with rats fed on maize starch.3. Female Sprague-Dawley rats were fed on the same three diets as the male rats, and mated when they weighed about 200 g. No difference was seen in their ability to mate, the progress of pregnancies, or the sizes of the litters. Does fed on unrefined sugar produced litters of higher viability than did does fed on starch or sucrose. Survival was between 85 and 100% with unrefined sugar and between 30 and 75% with starch or sucrose.4. Unrefined muscovado sugar has thus been shown to contain a factor required by female rats for the proper viability of their pups. This may be the same ‘Reproductive Factor R’ as that described by Wiesner & Yudkin (1951). In certain circumstances, unrefined muscovado sugar might therefore contribute to the nutritional value of a human diet, although in what circumstances, in what respect and to what extent it might do so, is by no means clear.

Estrogen enhances baroreflex control of heart rate in conscious ovariectomized rats

1998 ◽  
Vol 76 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Mahmoud M El-Mas ◽  
Abdel A Abdel-Rahman
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Sprague Dawley ◽  
Baroreflex Control ◽  
Baroreflex Function ◽  
Vehicle Treatment

In previous studies, we have shown that the baroreflex control of heart rate is significantly attenuated in females compared with age-matched males. This study investigated the role of estrogen in the modulation of baroreflex function in conscious unrestrained rats. Baroreflex-mediated decreases in heart rate in response to increments in blood pressure evoked by phenylephrine were evaluated in conscious freely moving male and female Sprague-Dawley rats as well as in ovariectomized rats. The effect of a 2-day 17 beta -estradiol (50 µg ·kg-1 ·day-1, s.c.) or vehicle treatment on baroreflex sensitivity was investigated in ovariectomized rats. Intravenous bolus doses of phenylephrine (1-16 µg/kg) elicited dose-dependent pressor and bradycardic responses in all groups of rats. Regression analysis of the baroreflex curves relating increments in blood pressure to the associated heart rate responses revealed a significantly (p < 0.05) smaller baroreflex sensitivity in female compared with male rats (-1.22 ± 0.07 and -1.85 ± 0.15 beats ·min-1 ·mmHg-1, respectively), suggesting an attenuated baroreflex function in females. In age-matched ovariectomized rats, baroreflex sensitivity showed further reduction (-0.93 ± 0.02 beats ·min-1 ·mmHg-1). Treatment of ovariectomized rats with 17 beta -estradiol significantly (p < 0.05) enhanced the baroreflex sensitivity (-1.41 ± 0.16 beats ·min-1 ·mmHg-1) to a level that was slightly higher than that of sham-operated female rats. Furthermore, baroreflex sensitivity of ovariectomized estradiol-treated rats was not significantly different from that of age-matched male rats. The vehicle, on the other hand, had no effect on baroreflex sensitivity of ovariectomized rats. These data support our earlier findings that sexual dimorphism exists in baroreflex control of heart rate. More importantly, the present study provides experimental evidence that suggests a facilitatory role for estrogen in the modulation of baroreflex function.Key words: rat, gender, baroreflex sensitivity, 17 beta -estradiol, ovariectomy.

ROLE OF THE GONADS IN THE REGULATION OF SEBACEOUS GLANDS IN RATS: COMPARISON OF THE EFFECTS OF CASTRATION AT AND AFTER BIRTH

1980 ◽  
Vol 85 (2) ◽  
pp. 261-265 ◽  
Author(s):  
YEE CHU TOH
Keyword(s):  
Skin Surface ◽  
Female Rats ◽  
Sprague Dawley ◽  
Sebaceous Glands ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Sequential Event ◽  
Sebum Production ◽  
Skin Surface Lipids

Sprague–Dawley rats were castrated either within 24 h of birth or at 4 weeks of age. Control animals were sham operated. Intact female rats were also included for comparison. Sebum production was assessed at 80 days of age by measuring the amount of skin-surface lipids that could be extracted with acetone and which had been produced during 2 days. The removal of the testes at birth reduced the activity of the sebaceous glands to a level more nearly approaching that seen in the female rats whereas castration at 4 weeks of age only partially decreased the rate of sebum secretion so that it was intermediate between the male and female rats. The weights of the pituitary gland, thyroid and adrenal glands increased after castration but there were no differences between rats castrated at birth and those castrated at 4 weeks of age except in the weight of the thyroid gland. It would appear that the role of the testes in the control of the activity of the sebaceous glands is a sequential event which has already started at birth.

scholarly journals Intraperitoneal Alfaxalone and Alfaxalone–Dexmedetomidine Anesthesia in Sprague–Dawley Rats (Rattus norvegicus)

2020 ◽  
Vol 59 (5) ◽  
pp. 531-538
Author(s):  
Sylvia E West ◽  
Jonathan C Lee ◽  
Tinika N Johns ◽  
Elizabeth A Nunamaker
Keyword(s):  
Rattus Norvegicus ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Withdrawal Reflex ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Laboratory Rodent ◽  
Physiologic Parameters

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.

scholarly journals Contribution of cytochrome P-450 4A1 and 4A2 to vascular 20-hydroxyeicosatetraenoic acid synthesis in rat kidneys

1999 ◽  
Vol 276 (2) ◽  
pp. F246-F253 ◽  
Author(s):  
Mong-Heng Wang ◽  
Hui Guan ◽  
Xuandai Nguyen ◽  
Barbara A. Zand ◽  
Alberto Nasjletti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Rat Kidney ◽  
Acid Synthesis ◽  
Biologically Active ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Antisense Odns ◽  
Cytochrome P 450

20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active cytochrome P-450 (CYP) metabolite of arachidonic acid in the rat kidney, can be catalyzed by CYP4A isoforms including CYP4A1, CYP4A2, and CYP4A3. To determine the contribution of CYP4A isoforms to renal 20-HETE synthesis, specific antisense oligonucleotides (ODNs) were developed, and their specificity was examined in vitro in Sf9 cells expressing CYP4A isoforms and in vivo in Sprague-Dawley rats. Administration of CYP4A2 antisense ODNs (167 nmol ⋅ kg body wt−1 ⋅ day−1iv for 5 days) decreased vascular 20-HETE synthesis by 48% with no effect on tubular synthesis, whereas administration of CYP4A1 antisense ODNs inhibited vascular and tubular 20-HETE synthesis by 52 and 40%, respectively. RT-PCR of microdissected renal microvessel RNA indicated the presence of CYP4A1, CYP4A2, and CYP4A3 mRNAs, and a CYP4A1-immunoreactive protein was detected by Western analysis of microvessel homogenates. Blood pressure measurements revealed a reduction of 17 ± 6 and 16 ± 4 mmHg in groups receiving CYP4A1 and CYP4A2 antisense ODNs, respectively. These studies implicate CYP4A1 as a major 20-HETE synthesizing activity in the rat kidney and further document the feasibility of using antisense ODNs to specifically inhibit 20-HETE synthesis and thereby investigate its role in the regulation of renal function and blood pressure.

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