Pregnancy influence on the vascular interactions between nitric oxide and other endothelium-derived mediators in rat kidney

2003 ◽  
Vol 81 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Rosa A Bobadilla ◽  
Liliana Anguiano ◽  
Victor Pérez-Alvarez ◽  
Pedro López Sanchez
Keyword(s):  
Nitric Oxide ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Renal Perfusion ◽  
Enos Expression ◽  
Response Curves ◽  
Synthesis Inhibitor ◽  
Pregnant Rats ◽  
Vasoactive Mediators ◽  
Cox 1

Peripheral vascular resistance and sensitivity to circulating pressor and vasoconstrictor agents are blunted during pregnancy. This has been mainly attributed to an increased production of endothelium-derived mediators. The objective of this work was to evaluate if pregnancy changes the relative participation of nitric oxide (NO) and prostaglandins (PG) in respect to the modulation of the increases in renal perfusion pressure induced by phenylephrine (Phe). Dose–response curves were made with gradually increasing doses of Phe using an isolated kidney preparation in the presence of a NO synthase (NOS) inhibitor (L-NAME, 1 μM), a PG-synthesis inhibitor (indomethacin, 1 μM), both, or neither. Also, renal cyclooxygenase (COX-1 and COX-2) and endothelial NOS (eNOS) expression was determined using PCR. The experiments were done in kidneys from nonpregnant and pregnant rats. Our results showed that the relative participation of renal vasoactive mediators seems to change during pregnancy. We found the presence of a COX-1-dependent vasoconstrictor in the middle of pregnancy that was not found in nonpregnant rats. Our results also suggest that there is increased participation of another renal vasodilator substance, the effect of which is observed when NO or PG synthesis is inhibited during late pregnancy. In addition, an apparent interaction between renal eNOS and COX-1 expression was observed: eNOS expression was diminished, while COX-1 was increased during the 2nd week of pregnancy. In contrast, in kidneys from the 3rd week of pregnancy, the expression of these two enzymes was similar.Key words: pregnancy, nitric oxide, prostaglandins, EDHF, kidney.

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.

Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II

1993 ◽  
Vol 265 (5) ◽  
pp. F651-F659 ◽  
Author(s):  
R. J. Barrett ◽  
D. A. Droppleman
Keyword(s):  
Nitric Oxide ◽  
Dose Response ◽  
Rat Kidney ◽  
Maximal Response ◽  
Ang Ii ◽  
Response Curves ◽  
Renal Vasoconstriction ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Synthase Inhibitor

Renal vasoconstrictor responses to the adenosine A1 agonist N6-cyclopentyladenosine (CPA) were compared in the in situ autoperfused rat kidney to responses evoked by angiotensin II (ANG II), endothelin-1 (ET-1), arginine vasopressin (AVP), carbocyclic thromboxane A2 (CTxA2), phenylephrine (PE), and 5-hydroxytryptamine (5-HT). On the basis of their ED50 values (dose of agonist, in mass units, that produced 50% of maximal response to that agonist), the order of vasoconstrictor potency was ANG II > or = AVP > ET-1 > CPA > 5-HT > or = PE > CTxA2. Dose-response curves to CPA were shallower and maximal responses were weaker than those produced by the other agonists. Maximal responses, the log ED50, and the slope of the dose-response curve to CPA were markedly potentiated in the presence of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Selective antagonism of A1 receptors increased renal blood flow and markedly attenuated CPA-induced renal vasoconstriction in the absence or presence of L-NAME but had no effect on the maximal responses to ANG II. Conversely, AT1 receptor antagonism attenuated renal vasoconstriction produced by ANG II but had little effect on the produced by CPA. These results suggest that endogenous NO modulates renal vasoconstriction produced by A1 receptor stimulation and provide evidence against an interaction between renovascular adenosine A1 and angiotensin AT1 receptors.

scholarly journals Effect of insulin on glucose metabolism in adipocytes from virgin and late-pregnant rats

1984 ◽  
Vol 224 (2) ◽  
pp. 685-688 ◽  
Author(s):  
A Leturque ◽  
M Guerre-Millo ◽  
M Lavau ◽  
J Girard
Keyword(s):  
Glucose Metabolism ◽  
High Sensitivity ◽  
Late Pregnancy ◽  
Maximal Response ◽  
Maximal Effect ◽  
Insulin Stimulation ◽  
Response Curves ◽  
Pregnant Rats

Under basal conditions (zero insulin), paraovarian adipocytes from 19-day-pregnant rats exhibited the same rates of [U-14C]glucose conversion into CO2 and total lipids as did those from age-matched virgin rats. The dose-response curves for insulin stimulation of glucose metabolism were similar in both groups: maximal response (+100% over basal values) and high sensitivity (half-maximal effect at 0.05 nM-insulin). The present results suggest that the insulin resistance in vivo that occurs during late pregnancy may involve circulating factors lost in vitro.

Increased endothelium-dependent renal vasodilation in cirrhotic rats

1994 ◽  
Vol 267 (2) ◽  
pp. R549-R553 ◽  
Author(s):  
J. Garcia-Estan ◽  
N. M. Atucha ◽  
J. M. Sabio ◽  
F. Vargas ◽  
T. Quesada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Liver Cirrhosis ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
High Dose ◽  
Dependent Manner ◽  
Response Curves ◽  
Renal Perfusion Pressure ◽  
Dose Dependent

We have evaluated the renal blood flow (RBF) response of cirrhotic rats to endothelium-dependent [acetylcholine (ACh)] and -independent [sodium nitroprusside (NP)] vasodilators. In anesthetized rats, ACh dose dependently increased RBF, but the response of the cirrhotic rats (n = 6) was significantly higher than that of the controls (n = 6). NP also increased RBF in a dose-dependent manner, but there were no differences between both groups. NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg i.v.) significantly reduced the responses to ACh in both groups, but those of the cirrhotic rats were still higher than those of the controls. In experiments performed in isolated perfused kidneys, preconstricted with phenylephrine, dose-response curves for ACh and NP were obtained in the presence of indomethacin. Both ACh and NP decreased renal perfusion pressure dose dependently, but only the response of the cirrhotic rats (n = 5) to ACh was significantly higher than that of the controls (n = 5). L-NAME (100 microM) significantly reduced the responses to ACh and increased those of NP and abolished the differences between groups, except at the high dose of ACh. These results demonstrate an elevated endothelium-dependent vasodilator response in the cirrhotic kidney, which is eliminated by combined prostaglandin and nitric oxide (NO) synthesis inhibition and suggest that increased intrarenal activity of NO may be contributing to the renal alterations of liver cirrhosis.

Blockade of pressure natriuresis induced by inhibition of renal synthesis of nitric oxide in dogs

1992 ◽  
Vol 262 (5) ◽  
pp. F718-F722 ◽  
Author(s):  
M. G. Salom ◽  
V. Lahera ◽  
F. Miranda-Guardiola ◽  
J. C. Romero
Keyword(s):  
Nitric Oxide ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Inhibitory Effect ◽  
Synthesis Inhibitor ◽  
Urine Sodium ◽  
Water Excretion ◽  
Anesthetized Dogs ◽  
Pressure Natriuresis ◽  
Acute Changes

To evaluate the participation of nitric oxide (NO) on pressure-induced natriuresis in pentobarbital-anesthetized dogs, renal perfusion pressure (RPP) was increased twice from 100 to 150 mmHg before and during the intrarenal administration of an NO-synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), while determining changes in glomerular filtration rate (GFR), renal blood flow (RBF), and urine sodium and water excretion. Before the inhibition of NO, the increase in RPP induced diuresis (5-fold) and natriuresis (4.2-fold) with no change in RBF or GFR. However, the intrarenal infusion of L-NAME (1 microgram.kg-1.min-1) blunted the diuretic and natriuretic responses without altering RBF or GFR. The infusion of the NO synthesis precursor L-arginine prevented the inhibitory effect that L-NAME exerted on the diuretic and natriuretic responses to the increase in RPP. These results indicate that the increase in RPP stimulates NO synthesis and suggest that NO might play an important role in the control of sodium and water excretion during acute changes in RPP.

scholarly journals Reductions of Circulating Nitric Oxide are Followed by Hypertension during Pregnancy and Increased Activity of Matrix Metalloproteinases-2 and -9 in Rats

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1402 ◽  
Author(s):  
Regina A. Nascimento ◽  
Jose S. Possomato-Vieira ◽  
Giselle F. Bonacio ◽  
Elen Rizzi ◽  
Carlos A. Dias-Junior
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Matrix Metalloproteinases ◽  
Late Pregnancy ◽  
Placental Development ◽  
Pregnant Rats ◽  
Hypertensive Pregnancy ◽  
No Bioavailability ◽  
Late Stages ◽  
Increased Activity

Hypertensive pregnancy has been associated with reduced nitric oxide (NO), bioavailability, and increased activity of matrix metalloproteinases (MMPs). However, it is unclear if MMPs activation is regulated by NO during pregnancy. To this end, we examined activity of MMP-2 and MMP-9 in plasma, placenta, uterus and aorta, NO bioavailability, oxidative stress, systolic blood pressure (SBP), and fetal-placental development at the early, middle, and late pregnancy stages in normotensive and Nω-Nitro-L-arginine methyl-ester (L-NAME)-induced hypertensive pregnancy in rats. Reduced MMP-2 activity in uterus, placenta, and aorta and reduced MMP-9 activity in plasma and placenta with concomitant increased NO levels were found in normotensive pregnant rats. By contrast, increased MMP-2 activity in uterus, placenta, and aorta, and increased MMP-9 activity in plasma and placenta with concomitant reduced NO levels were observed in hypertensive pregnant rats. Also, elevated oxidative stress was displayed by hypertensive pregnant rats at the middle and late stages. These findings in the L-NAME-treated pregnant rats were also followed by increases in SBP and associated with fetal growth restrictions at the middle and late pregnancy stages. We concluded that NO bioavailability may regulate MMPs activation during normal and hypertensive pregnancy.

Augmentation of baroreflex-mediated bradycardia in conscious pregnant rats

1992 ◽  
Vol 262 (3) ◽  
pp. R472-R477 ◽  
Author(s):  
K. P. Conrad ◽  
R. D. Russ
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sodium Nitroprusside ◽  
Dose Response ◽  
Late Pregnancy ◽  
Response Curves ◽  
Pregnant Rats ◽  
Baroreflex Control ◽  
Time Control ◽  
The Right

The goal of the present study was to examine baroreflex control of heart rate during pregnancy in chronically instrumented unrestrained rats. The same rats (n = 6) were studied before conception, again on gestational days 5, 12, and 19, and last on postpartum day 6; thus each rat served as its own control. Time control experiments were also conducted in a separate group of virgin rats (n = 7). Resting mean arterial pressure decreased by 10 mmHg on gestational day 19 (P less than 0.01 vs. prepregnant), and heart rate significantly increased by approximately 10% relative to time control rats. Dose-response curves were constructed for methoxamine and sodium nitroprusside comparing the various dosages with systemic pressor and depressor responses, respectively. The dose-response relationship for methoxamine was shifted to the right in gravid rats of 19 gestational days (P less than 0.03 vs. prepregnant), indicating an attenuation of alpha-adrenergic receptor-mediated pressor responsiveness. In contrast, depressor responses to sodium nitroprusside were not significantly altered in pregnancy. Baroreflex-mediated bradycardia was unchanged until gestational day 19, when enhanced bradycardia responses to methoxamine were observed. Baroreflex-mediated tachycardic responses elicited by sodium nitroprusside were not affected at any stage of pregnancy. Baroreflex control of heart rate did not change significantly with either increases or decreases of blood pressure in time control experiments. We conclude that during late pregnancy in conscious rats 1) resting blood pressure decreases and heart rate increases, 2) systemic pressor responses to methoxamine are diminished, and 3) baroreflex-mediated bradycardia is enhanced.

scholarly journals Cyclooxygenase-dependent mechanisms mediate in part the anti-dilatory effects of perivascular adipose tissue in uterine arteries from pregnant rats

2021 ◽  
Author(s):  
Oluwatobiloba Osikoya ◽  
Spencer C. Cushen ◽  
Styliani Goulopoulou
Keyword(s):  
Adipose Tissue ◽  
Selective Inhibition ◽  
Response Curves ◽  
Pregnant Rats ◽  
Perivascular Adipose Tissue ◽  
Uterine Arteries ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Relaxation Responses ◽  
Cox 1

AbstractUterine perivascular adipose tissue (PVAT) contributes to uterine blood flow regulation in pregnancy, at least in part, due to its effects on uterine artery reactivity. Here, we investigated the effects of uterine PVAT on endothelium-dependent pathways involved in relaxation of main uterine arteries. We hypothesized that uterine PVAT modulates the balance between the contribution of nitric oxide synthase (NOS)- and cyclooxygenase (COX)-dependent pathways to acetylcholine (ACh)-induced relaxation in isolated uterine arteries. Concentration-response curves to ACh (1 nM – 30 µM) were performed on main uterine arteries from pregnant and non-pregnant rats. Arteries were exposed to Krebs-Henseleit solution (control) or PVAT-conditioned media (PVATmedia) in the presence of the following inhibitors: L-NAME (100 µM), indomethacin (COX inhibitor, 10 µM), SC560 (selective COX-1 inhibitor, 1 µM), NS398 (selective COX-2 inhibitor, 1 µM), SQ 29,548 (selective thromboxane receptor (TP) inhibitor, 1 µM). Indomethacin suppressed ACh-induced relaxation in control uterine arteries from pregnant rats (p<0.0001) but not in non-pregnant rats (p>1.0). In arteries incubated with PVATmedia, the presence of indomethacin increased ACh-induced relaxation, reversing the anti-dilatory effect of PVATmedia. NOS inhibition reduced ACh-induced relaxation in uterine arteries from pregnant rats, and exposure to PVATmedia did not change this effect. Selective inhibition of COX-1 but not COX-2 suppressed relaxation responses to ACh in control arteries. The presence of PVATmedia abolished the effect COX-1 inhibition. Incubation of uterine arteries from pregnant rats with PVATmedia increased production of thromboxane B2 (TxB2, p=0.01). TP inhibition did not have any effect on the anti-dilatory properties of PVATmedia. In conclusion, uterine PVAT releases transferable factors that reduce relaxation responses to ACh via a COX-dependent mechanism in isolated uterine arteries from pregnant rats.

Abstract P224: Cyclooxygenase-dependent Mechanisms Mediate In Part The Anti-dilatory Effects Of Uterine Perivascular Adipose Tissue In Rat Pregnancy

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Oluwatobiloba OSIKOYA ◽  
Spencer C Cushen ◽  
Styliani Goulopoulou
Keyword(s):  
Adipose Tissue ◽  
Physiological Salt Solution ◽  
Response Curves ◽  
Pregnant Rats ◽  
Perivascular Adipose Tissue ◽  
Uterine Arteries ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Relaxation Responses ◽  
Cox 1

Introduction: Uterine perivascular adipose tissue (PVAT) contributes to uterine blood flow regulation in pregnancy, at least in part, due to its effects on uterine artery tone. We hypothesized that the anti-dilatory effects of uterine PVAT are mediated by vascular nitric oxide synthase (NOS)- and cyclooxygenase (COX)-dependent mechanisms. Methods: Main uterine arteries from pregnant and non-pregnant rats were mounted onto a wire myograph. Concentration-response curves to acetylcholine (ACh, 10 -9 - 3x10 -5 M) were performed on arteries exposed to physiological salt solution or PVAT-conditioned media (PVAT media ) in the presence of the following inhibitors: a) L-NAME (NOS inhibitor, 100 μM), b) indomethacin (COX inhibitor, 10 μM), c) SC560 (COX-1 inhibitor, 1 μM), d) NS398 (COX-2 inhibitor, 1 μM)]. Results: NOS inhibition abolished ACh-induced relaxation in uterine arteries from pregnant rats and exposure to PVAT media did not change this effect [AUC, (-)PVAT media : 244.6 ± 18.1 vs. (-)PVAT media /(+)L-NAME: 52.64 ± 7.4, p < 0.0001; (+)PVAT media : 202.4 ± 15.5 vs. (+)PVAT media /(+)L-NAME: 56.17 ± 11.3, p < 0.0001]. Indomethacin suppressed ACh-induced relaxation in uterine arteries from pregnant rats [AUC, (-)PVAT media : 243.6 ± 6.6 vs. (-)PVAT media /(+)Indomethacin: 123.6 ± 12.3, p < 0.0001] but not in non-pregnant rats (p>1.0). In arteries incubated with PVAT media , the presence of indomethacin increased ACh-induced relaxation [AUC, (+)PVAT media : 125.2 ± 11.4 vs. (+)PVAT media /(+)Indomethacin: 179.1 ± 14.7, p = 0.01]. COX-1 but not COX-2 inhibition suppressed relaxation responses to ACh [AUC, COX-1 inhibition, (-)PVAT media : 244.6 ± 12.0 vs. (-)PVAT media /(+)SC560: 142.4 ± 15.4, p = 0.02; COX-2 inhibition, (-)PVAT media vs. (-)PVAT media /(+)NS398, p=0.1). The anti-dilatory effects of PVAT were not observed in the presence of SC560 or NS398 (p>0.05). Exposure to PVAT media increased the protein content of COX-1 (p=0.05) and COX-2 (p=0.03) and the production of thromboxane B 2 (p=0.01) in uterine arteries from pregnant rats. Conclusion: The anti-dilatory effects of PVAT-derived factors on uterine arteries are mediated in part by COX-derived products and this mechanism is specific to pregnancy.

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