scholarly journals Glomerular hemodynamic effects of late pregnancy in rats with experimental membranous glomerulonephropathy.

1995 ◽  
Vol 6 (4) ◽  
pp. 1197-1201
Author(s):  
C Baylis ◽  
A Deng ◽  
W G Couser
Keyword(s):  
Blood Pressure ◽  
Late Pregnancy ◽  
Systemic Blood Pressure ◽  
Female Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Heymann Nephritis ◽  
Single Nephron ◽  
Glomerular Capillary Hypertension ◽  
Membranous Glomerulonephropathy

In these studies, the Fx1A model of accelerated, passive Heymann nephritis was used to produce membranous glomerulonephropathy. Female rats were studied at 7 wk after the administration of the Fx1A antibody either in the virgin state or in late pregnancy. The goals of these experiments were to determine whether preexisting membranous glomerulonephropathy compromises the pregnancy and whether the pregnancy acutely worsens the renal function. Virgin rats with membranous glomerulonephropathy developed massive proteinuria and exhibited glomerular capillary hypertension but without declines in GFR. In late pregnancy, there was no worsening of the proteinuria and glomerular blood pressure fell to normal values. Both afferent and efferent arteriolar resistances increased in pregnant rats with membranous glomerulonephropathy compared with virgins, leading to falls in glomerular plasma flow and single-nephron GFR. There were no histologic abnormalities in the glomeruli of either virgin or late pregnant rats with membranous glomerulonephropathy, and both groups exhibited similar immunoglobulin G and complement deposits. Up to Day 19 (term is 22 days), the pregnancy in rats with membranous glomerulonephropathy appeared uneventful. Thus, this study indicates that the Fx1A model of membranous glomerulonephropathy does not compromise the course of the pregnancy, at least until close to term. Pregnancy lowers glomerular blood pressure in rats with membranous glomerulonephropathy because of both a fall in systemic blood pressure and the atypical renal vasoconstriction, which leads to declines in single-nephron GFR.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

Glomerular dynamics and salt balance in pregnant rats with renal hypertension

1989 ◽  
Vol 256 (4) ◽  
pp. F728-F734 ◽  
Author(s):  
A. Dal Canton ◽  
M. Altomonte ◽  
G. Conte ◽  
C. Esposito ◽  
G. Fuiano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Hypertension ◽  
Chronic Hypertension ◽  
Marked Rise ◽  
Pregnant Rats ◽  
Hypertension In Pregnancy ◽  
Single Nephron ◽  
Renal Micropuncture ◽  
Glomerular Hemodynamics ◽  
Goldblatt Hypertension

These studies were aimed at investigating whether chronic hypertension in pregnancy causes changes both in salt excretion (NaE) and in glomerular hemodynamics. Metabolic and renal micropuncture studies were performed in pregnant (P) and Virgin (V) Munich-Wistar rats with normal blood pressure (N) and two-kidney Goldblatt hypertension (H). Mean NaE was higher in PN than VN (2.7 vs. 1.7 meq/day, P less than 0.01). Hypertension raised NaE both in P and V rats: in P and V rats with "benign" hypertension (blood pressure less than 180 mmHg) NaE averaged 3.2 and 2.6 meq/day, respectively (P less than 0.05); mean NaE was 5.9 and 3.8 meq/day, respectively (P less than 0.01), in P and V rats with "malignant" hypertension (blood pressure greater than or equal to 180 mmHg). Afferent arteriole resistance (Ra) averaged 1.73 and 3.50 10 dyn.s-1.cm5 in PN and VN, respectively (P less than 0.01). Hypertension raised Ra in V, but not in P rats (4.47 vs. 2.14 10 dyn.s-1.cm5, P less than 0.01). Thus glomerular plasma flow, glomerular capillary hydrostatic pressure, and single-nephron glomerular filtration rate were markedly higher in PH than VH rats: in PH rats single-nephron filtration fraction was significantly lower than in VH. These results show that in PH rats a marked rise in NaE is associated with glomerular vasodilation.

Calcium channels contribute to the decrease in blood pressure of pregnant rats

2002 ◽  
Vol 282 (2) ◽  
pp. H665-H671 ◽  
Author(s):  
May Simaan ◽  
Chanterelle Cadorette ◽  
Matthieu Poterek ◽  
Jean St-Louis ◽  
Michèle Brochu
Keyword(s):  
Blood Pressure ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Plasma Renin ◽  
Late Pregnancy ◽  
Pregnant Rats ◽  
Affect Body Weight ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Calcium Channel Activator

Pregnancy is associated with hemodynamic changes such as reduced vascular resistance and blood pressure. We reported that, during late pregnancy, the activity of voltage-dependent calcium channels (VDCC) is altered in the adrenal cortex and vascular smooth muscle. These observations suggested that the late pregnancy-induced decrease in blood pressure is linked to diminished VDCC function. We attempted to prevent pregnancy-induced reduced blood pressure with a calcium channel activator (CGP 28392) in pregnant rats and to mimic it by administration of a calcium channel blocker (nifedipine) to nonpregnant rats. Treatment was given from the 15th day of gestation for 7 days. The systolic blood pressure of CGP 28392-treated pregnant rats rose transiently for 2 days and then declined toward values of nontreated pregnant controls, although remaining higher. However, nonpregnant rats maintained their high arterial pressure throughout CGP 28392 treatment. Nifedipine lowered the blood pressure in nonpregnant rats to values of nontreated term-pregnant controls. Both agents did not affect body weight, water or food intake, plasma renin activity, and plasma aldosterone or corticosterone levels. Nifedipine and CGP 28392 treatment of nonpregnant and pregnant animals, respectively, did not modify the response of aortic rings to KCl. These results show that VDCC activation caused hypertension, which modified the extent of the decrease in blood pressure at the end of pregnancy.

The plasma pattern of growth hormone in conscious rats during late pregnancy

1990 ◽  
Vol 124 (2) ◽  
pp. 191-198 ◽  
Author(s):  
L. Carlsson ◽  
S. Edén ◽  
J.-O. Jansson
Keyword(s):  
Late Pregnancy ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Female Rats ◽  
Pregnant Rats ◽  
Fourfold Increase ◽  
Pregnant Females ◽  
Basal Plasma ◽  
Analysis Computer ◽  
Plasma Gh

ABSTRACT The plasma GH levels of female rats during late pregnancy were determined using an automatic method for repetitive blood sampling from conscious animals. The plasma GH patterns were analysed by a pulse analysis computer program (PULSAR). The mean plasma GH levels were about twofold higher in pregnant females on days 15, 18 and 22 of gestation than in age-matched non-pregnant females. The basal plasma GH levels were also increased, while there was no change in GH pulse amplitude or frequency. The augmentation of GH release was even more pronounced on day 20 of gestation, with a fourfold increase in mean plasma GH levels compared with those in non-pregnant females. This increase reflected an increase in both basal plasma GH levels and GH pulse amplitude, but there was no increase in pulse frequency. In female rats that delivered on day 22 of gestation, the basal and mean plasma GH levels increased during parturition. Pregnant females consistently responded to multiple i.v. infusions of 1 μg human GH-releasing factor analogue (hGRF(1–29)-NH2) given at 45-min intervals on day 18 of gestation. Both basal and GRF analogue-stimulated plasma GH levels were undetectable after hypophysectomy of pregnant rats. The present study demonstrates an increase in basal plasma GH levels during late pregnancy and a marked increase in both basal plasma GH levels and GH pulse amplitude on day 20 of gestation. Furthermore, hypophysectomy of pregnant rats results in undetectable GH levels, indicating that the high levels of GH during pregnancy are derived from the pituitary. Journal of Endocrinology (1990) 124, 191–198

Abstract 273: Increased Blood Pressure and Proteinuria and Absence of Increased Nitric Oxide (NO) Production During Pregnancy in the Dahl Salt Sensitive (S) Rat

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ellen E Gillis ◽  
Jennifer N Mooney ◽  
Jan M Williams ◽  
Michael R Garrett ◽  
Jennifer M Sasser
Keyword(s):  
Blood Pressure ◽  
Genetic Model ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
Kidney Cortex ◽  
No Production ◽  
Pregnant Rats ◽  
Telemetry Unit ◽  
Nos Inhibitor ◽  
Volume Retention

In normal pregnancy, systemic vasodilation due to increased NO production allows a drop in blood pressure (BP) despite increased volume retention. Little is known about the pathogenesis of preeclampsia, defined by increased BP and proteinuria, due to a lack of animal models that spontaneously develop the disease. Here we tested the hypothesis that the Dahl S rat, a genetic model of hypertension and kidney disease, is also a spontaneous model of preeclampsia. Female Dahl S rats were implanted with a telemetry unit, and baseline BP was recorded. Rats were placed in metabolic cages for 24 hr urine collection while on a low nitrate diet, and urinary protein and NO metabolite concentrations were measured via Bradford and Greiss assays, respectively. There were no differences in baseline BP (152±1 vs 151±4 mmHg) or proteinuria (61±10 vs 60±17 mg/d) in the rats selected for mating vs virgin rats (n=5-7). Pregnancy was confirmed by presence of sperm (day 1). Measurements were made during mid and late pregnancy (days 10-11, 17-18), and terminal measurements were taken on day 19. Pregnant rats exhibited an increase in BP and proteinuria with no change in urinary NOx excretion (Table), while no changes were observed in age-matched virgin rats. Kidney cortex abundance of neither NOS1 nor NOS3 was increased at late pregnancy; however, plasma concentration of the endogenous NOS inhibitor ADMA was increased in late pregnant compared to virgin rats (0.82±0.06 vs. 0.62±0.06 μM, p<0.05). These data suggest that the Dahl S rat cannot upregulate NO production during pregnancy; therefore, this relative NO deficiency may contribute to worsening hypertension and proteinuria during pregnancy in this strain.

scholarly journals Renal epoxyeicosatrienoic acid synthesis during pregnancy

2005 ◽  
Vol 288 (1) ◽  
pp. F221-F226 ◽  
Author(s):  
Yiqiang Zhou ◽  
Hsin-Hsin Chang ◽  
Juan Du ◽  
Cong-Yi Wang ◽  
Zheng Dong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Immunohistochemical Analysis ◽  
Acid Synthesis ◽  
The Body ◽  
Female Rats ◽  
Epoxyeicosatrienoic Acid ◽  
Pregnant Rats ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Renal Tubular

Epoxyeicosatrienoic acids (EETs), which belong to cytochrome P-450 (CYP)-derived eicosanoids, have been implicated to vasodilate renal arterioles, inhibit sodium transport in the nephron, and regulate blood pressure in several animal models. Because pregnancy is associated with changes of blood pressure, the aim of this study was to examine whether renal EET synthesis is altered and whether EETs are involved in blood pressure regulation during pregnancy in rats. Renal microsomal epoxygenase activity increased by 47, 97, and 63% on days 6, 12, and 19 of gestation, respectively. The elevation of epoxygenase activity during pregnancy was associated with an increase in CYP2C11, CYP2C23, and CYP2J2 protein expression on days 6, 12, and 19 of gestation. Moreover, immunohistochemical analysis showed that renal tubular CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in pregnant rats on days 6, 12, and 19 of gestation. Administration of 6-(2-propargyloxyphenyl)hexanoic acid (PPOH), a selective epoxygenase inhibitor, caused a dose-dependent inhibition of microsomal expoxygenase activity without a significant effect on ω-hydroxylase activity in female rats. Interestingly, administration of PPOH (20 mg·kg−1·day−1 for 4 days starting on day 15 of pregnancy) increased blood pressure by 21 mmHg and caused a significant decrease in the body weight of fetal pups (1.3 ± 0.08 g in control vs. 1.1 ± 0.06 g in PPOH). Moreover, PPOH treatment significantly decreased renal microsomal epoxygenase activity and the expression of CYP2C11, CYP2C23, and CYP2J in pregnant rats. This study demonstrates that EET synthesis in the kidney is elevated during pregnancy, and CYP2C11, 2C23, and CYP2J2 are responsible for the change of renal EET synthesis. The inhibition results demonstrate that the downregulation of renal epoxygenase activity by PPOH causes hypertension in pregnant rats. This study suggests that EETs may contribute to the control of blood pressure during pregnancy.

scholarly journals Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure

2006 ◽  
Vol 188 (3) ◽  
pp. 435-442 ◽  
Author(s):  
P W F Hadoke ◽  
R S Lindsay ◽  
J R Seckl ◽  
B R Walker ◽  
C J Kenyon
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Adult Female ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Control Group ◽  
Pregnant Rats ◽  
Vascular Contractility

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 μg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12–16 weeks) of Dex-treated mothers (148.0 ± 3.6 mmHg, n=10) compared with the control group (138.0 ± 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 ± 3.6 mmHg) than in controls (135.3 ± 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.

Expression of multidrug resistance-associated protein 2 in small intestine from pregnant and postpartum rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1261-G1273 ◽  
Author(s):  
Aldo D. Mottino ◽  
Tim Hoffman ◽  
Lothar Jennes ◽  
Jingsong Cao ◽  
Mary Vore
Keyword(s):  
Small Intestine ◽  
Multidrug Resistance ◽  
Blot Analysis ◽  
Late Pregnancy ◽  
Female Rats ◽  
Intestinal Cell ◽  
Pregnant Rats ◽  
Control Female ◽  
Protein Levels ◽  
Pregnancy And Lactation

We analyzed the expression of multidrug resistance-associated protein 2 (mrp2) in the small intestine of control female rats and in rats during late pregnancy (19–20 days of pregnancy) and lactation (2–4, 10–14, and 21 days after delivery). Western blot analysis was performed on brush-border membranes prepared from different regions of the small intestine. Expression of mrp2 was maximal in the proximal segments for all experimental groups, was preserved in pregnant rats, and increased by 100% in postpartum rats by late lactation with respect to control animals. Northern blot analysis of mrp2 mRNA revealed a positive correlation with protein levels. Transport of S-glutathione-dinitrophenol (DNP-SG) from the intestinal cell to the lumen was analyzed in the everted intestinal sac model. Secretion of DNP-SG was not altered in pregnant rats but increased in lactating animals by late lactation. Intestinal mrp2 mRNA, protein, and transport activity are increased in lactating rats, suggesting that this may represent an adaptive mechanism to minimize the toxicity of dietary xenobiotics in response to increased postpartum food consumption.

Locally produced EDRF controls preglomerular resistance and ultrafiltration coefficient

1993 ◽  
Vol 264 (2) ◽  
pp. F212-F215 ◽  
Author(s):  
A. Deng ◽  
C. Baylis
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Significant Rise ◽  
Small Reduction ◽  
Renal Vasoconstriction ◽  
Relaxing Factor ◽  
Arterial Blood ◽  
Single Nephron ◽  
Glomerular Hemodynamics

During systemic acute blockade of endogenous endothelial-derived relaxing factor (EDRF) with N-monomethyl-L-arginine (NMA), a significant rise in arterial blood pressure (BP) occurred in the anesthetized rat. Renal vasoconstriction was also seen, with complex changes in glomerular hemodynamics; both preglomerular (RA) and efferent arteriolar (RE) resistances increased, producing a fall in glomerular plasma flow (QA) and a rise in glomerular blood pressure (PGC). The glomerular capillary ultrafiltration coefficient (Kf) was reduced. The net effect was a small fall in single-nephron glomerular filtration rate (SNGFR). To determine the effects of local EDRF blockade, two additional groups were studied with intrarenal administration of NMA; in the first series, one-tenth of the systemic dose was given, which produced no change in BP, a small renal vasoconstriction with an increase in RA, but no change in RE; thus PGC was unaffected. Kf fell, and a small reduction in SNGFR was seen. With a larger intrarenal dose of NMA (one-fifth systemic) a moderate rise in BP occurred, but only RA rose; RE and PGC were unaffected, and Kf and SNGFR fell. These observations suggest that locally produced EDRF controls RA and Kf and that a rise in RE and PGC is only seen with systemic EDRF blockade when a large rise in BP occurs.

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