Mechanisms of vasodilatation in pregnancy: studies of the role of prostaglandins and nitric-oxide in changes of vascular reactivity in the in situ blood perfused mesentery of pregnant rats

During pregnancy the pressor response to vasoconstrictor substances such as angiotensin II (ANG II) is diminished, and renal, uterine, and vascular prostaglandin (PG) production may increase. However, little is known about the factors that alter vascular reactivity or stimulate PG synthesis during pregnancy. To ascertain whether these factors are of maternal or fetal-placental origin, we studied vascular reactivity and urinary PGE excretion in pseudopregnant rats. Pseudopregnant rats had plasma progesterone and weight gain similar to that observed in pregnant rats. Urinary PG excretion in nonpregnant rats was approximately 70 ng/24 h and remained constant during a 12-day observation. In contrast, urinary PG excretion in both pregnant and in pseudopregnant rats rose to levels approximately twice control within 4-6 days. The pressor response to ANG II was diminished in pseudopregnant rats compared with nonpregnant rats. When the PG synthesis inhibitor meclofenamate was given there was no change in the pressor response to ANG II in nonpregnant animals, but in pseudopregnant animals meclofenamate produced a significant increase in the pressor response to ANG II. The pressor response to norepinephrine and arginine vasopressin (AVP) was not diminished in pseudopregnant animals, and meclofenamate did not increase the pressor response to these agents. Therefore, a developing fetus and placenta is not necessary for the decrease in pressor response to ANG II nor for the early increase in urinary PGE excretion. Like in pregnancy, the pressor response to ANG II was increased after meclofenamate in pseudopregnancy. Increased PG production may, therefore, be partly responsible for the decrease in pressor responsiveness to ANG II. However, pseudopregnancy, unlike pregnancy, did not affect pressor responsiveness to norepinephrine or AVP. Both maternal and fetal-placental factors seem required for the reduction in responsiveness to norepinephrine and AVP in pregnancy.

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Nitric Oxide and Vascular Reactivity in Pregnant Rats with Adriamycin Nephropathy

Clinical Science ◽

10.1042/cs0930227 ◽

1997 ◽

Vol 93 (3) ◽

pp. 227-234 ◽

Cited By ~ 3

Author(s):

Mauro Rathaus ◽

Eduardo Podjarny ◽

Sydney Benchetrit ◽

Janice Green ◽

Jacques Bernheim

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Vascular Reactivity ◽

Normal Pregnancy ◽

Pregnant Rats ◽

Arterial Blood ◽

Adriamycin Nephropathy ◽

Mesenteric Vessels

1. In previous studies we have shown that, after the administration of adriamycin, hypertension developed in rats who became pregnant (adriamycin-pregnant rats), whereas virgin animals remained normotensive. Subsequently, we showed that this hypertension was prevented by administration of l-arginine, suggesting that deficient synthesis of nitric oxide may be pathogenetic in this model. 2. To further assess the role of nitric oxide in this model, we measured mean arterial blood pressure after administration of l-arginine to adriamycin-pregnant rats or of NG-nitro-l-arginine-methyl ester (l-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arterial mesenteric vessels, precontracted with noradrenaline, to acetylcholine, l-arginine or l-NAME. 3. Blood pressure was decreased in normal pregnant rats, whereas it was elevated in adriamycin-pregnant rats. l-NAME treatment increased blood pressure in normal pregnant rats and l-arginine decreased it in adriamycin-pregnant rats. 4. Mesenteric vessels of adriamycin-pregnant rats exibited an exaggerated vasoconstrictory response to noradrenaline, when compared with the blunted response observed in normal pregnancy. The addition of l-NAME in vitro induced a further contraction, significantly greater in normal pregnant rats. The vasodilatory response to acetylcholine and l-arginine was greater in vessels from adriamycin-pregnant rats. In contrast, responses to either nitroprusside or diazoxide were similar in all groups. 5. The results suggest a state of reduced nitric oxide synthesis in rats with adriamycin nephropathy, leading to vascular maladaption and hypertension in pregnancy.

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Demonstration of the existence of nitric oxide-independent as well as nitric oxide-dependent vasodilator mechanisms in the in situ renal circulation in near term pregnant rats

British Journal of Pharmacology ◽

10.1038/sj.bjp.0701363 ◽

1997 ◽

Vol 122 (2) ◽

pp. 307-315 ◽

Cited By ~ 7

Author(s):

Z. M. Chu ◽

L. J. Beilin

Keyword(s):

Nitric Oxide ◽

Renal Circulation ◽

Pregnant Rats ◽

Near Term

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Nitric oxide synthase-mediated blood pressure regulation in obese melanocortin-4 receptor-deficient pregnant rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00285.2016 ◽

2016 ◽

Vol 311 (5) ◽

pp. R851-R857 ◽

Cited By ~ 3

Author(s):

Frank T. Spradley ◽

Jennifer M. Sasser ◽

Jacqueline B. Musall ◽

Jennifer C. Sullivan ◽

Joey P. Granger

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Mesenteric Arteries ◽

Elevated Blood Pressure ◽

Pressure Regulation ◽

Elevated Blood ◽

Pregnant Rats ◽

Melanocortin 4 Receptor ◽

Regulation Of Blood Pressure

Although obesity increases the risk for hypertension in pregnancy, the mechanisms responsible are unknown. Increased nitric oxide (NO) production results in vasodilation and reduced blood pressure during normal pregnancy in lean rats; however, the role of NO is less clear during obese pregnancies. We examined the impact of obesity on NO synthase (NOS)-mediated regulation of blood pressure during pregnancy by testing the hypothesis that NOS activity, expression, and regulation of vascular tone and blood pressure are reduced in obese pregnant rats. At gestational day 19, melanocortin-4 receptor (MC4R)-deficient obese rats (MC4R) had greater body weight and fat mass with elevated blood pressure and circulating sFlt-1 levels compared with MC4R pregnant rats. MC4R pregnant rats also had less circulating cGMP levels and reduced total NOS enzymatic activity and expression in mesenteric arteries. Despite decreased biochemical measures of NO/NOS in MC4R rats, NOS inhibition enhanced vasoconstriction only in mesenteric arteries from MC4R rats, suggesting greater NOS-mediated tone. To examine the role of NOS on blood pressure regulation in obese pregnant rats, MC4R and MC4R pregnant rats were administered the nonselective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 mg/l) from gestational day 14 to 19 in drinking water. The degree by which l-NAME raised blood pressure was similar between obese and lean pregnant rats. Although MC4R obese pregnant rats had elevated blood pressure associated with reduced total NOS activity and expression, they had enhanced NOS-mediated attenuation of vasoconstriction, with no evidence of alterations in NOS-mediated regulation of blood pressure.

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Central role of nitric oxide in ozone production in the upper tropical troposphere over the Atlantic Ocean and western Africa

Atmospheric Chemistry and Physics ◽

10.5194/acp-21-8195-2021 ◽

2021 ◽

Vol 21 (10) ◽

pp. 8195-8211

Author(s):

Ivan Tadic ◽

Clara M. Nussbaumer ◽

Birger Bohn ◽

Hartwig Harder ◽

Daniel Marno ◽

...

Keyword(s):

Nitric Oxide ◽

Atlantic Ocean ◽

General Circulation ◽

Simulated Data ◽

Ozone Production ◽

Mixing Ratios ◽

Western Africa ◽

Tropical Troposphere

Abstract. Mechanisms of tropospheric ozone (O3) formation are generally well understood. However, studies reporting on net ozone production rates (NOPRs) directly derived from in situ observations are challenging and are sparse in number. To analyze the role of nitric oxide (NO) in net ozone production in the upper tropical troposphere above the Atlantic Ocean and western Africa, we present in situ trace gas observations obtained during the CAFE-Africa (Chemistry of the Atmosphere: Field Experiment in Africa) campaign in August and September 2018. The vertical profile of in situ measured NO along the flight tracks reveals lowest NO mixing ratios of less than 20 pptv between 2 and 8 km altitude and highest mixing ratios of 0.15–0.2 ppbv above 12 km altitude. Spatial distribution of tropospheric NO above 12 km altitude shows that the sporadically enhanced local mixing ratios (>0.4 ppbv) occur over western Africa, which we attribute to episodic lightning events. Measured O3 shows little variability in mixing ratios at 60–70 ppbv, with slightly decreasing and increasing tendencies towards the boundary layer and stratosphere, respectively. Concurrent measurements of CO, CH4, OH, HO2 and H2O enable calculations of NOPRs along the flight tracks and reveal net ozone destruction at −0.6 to −0.2 ppbv h−1 below 6 km altitude and balance of production and destruction around 7–8 km altitude. We report vertical average NOPRs of 0.2–0.4 ppbv h−1 above 12 km altitude with NOPRs occasionally larger than 0.5 ppbv h−1 over western Africa coincident with enhanced NO. We compare the observational results to simulated data retrieved from the general circulation model ECHAM/MESSy Atmospheric Chemistry (EMAC). Although the comparison of mean vertical profiles of NO and O3 indicates good agreement, local deviations between measured and modeled NO are substantial. The vertical tendencies in NOPRs calculated from simulated data largely reproduce those from in situ experimental data. However, the simulation results do not agree well with NOPRs over western Africa. Both measurements and simulations indicate that ozone formation in the upper tropical troposphere is NOx limited.

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The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

Sao Paulo Medical Journal ◽

10.1590/s1516-31801999000500004 ◽

1999 ◽

Vol 117 (5) ◽

pp. 197-204 ◽

Cited By ~ 7

Author(s):

Nilton Hideto Takiuti ◽

Maria Helena Cetelli Carvalho ◽

Soubhi Kahhale ◽

Dorothy Nigro ◽

Hermes Vieira Barbeiro ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Vascular Reactivity ◽

Unit Weight ◽

Control Group ◽

Pregnant Rats ◽

Nitric Oxide Inhibition ◽

Female Wistar Rats ◽

Main Component ◽

Oxide Inhibition

CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF) and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams) and age (90 to 116 days). INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats); pregnant control rats (8 rats); virgin rats treated with L-NAME (10 rats); virgin control rats (12 rats). The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME), in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.

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Roles of Nitric Oxide and Prostaglandins in the Sustained Antihypertensive Effects of Acanthospermum hispidum DC. on Ovariectomized Rats with Renovascular Hypertension

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/2492483 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 2

Author(s):

Rhanany Alan Calloi Palozi ◽

Maysa Isernhagen Schaedler ◽

Cleide Adriane Signor Tirloni ◽

Aniely Oliveira Silva ◽

Francislaine Aparecida dos Reis Lívero ◽

...

Keyword(s):

Nitric Oxide ◽

Renovascular Hypertension ◽

Vascular Reactivity ◽

Nitrosative Stress ◽

Folk Medicine ◽

Thiobarbituric Acid ◽

Ovariectomized Rats ◽

Oxidative And Nitrosative Stress ◽

Antihypertensive Response

Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery. Enalapril (15 mg/kg) and hydrochlorothiazide (25 mg/kg) were used as standard drugs. Diuretic activity was evaluated on days 1, 7, 14, 21, and 28. Systolic, diastolic, and mean blood pressure and heart rate were recorded. Serum creatinine, urea, thiobarbituric acid reactive substances, nitrosamine, nitrite, aldosterone, vasopressin levels, and ACE activity were measured. The vascular reactivity and the role of nitric oxide (NO) and prostaglandins (PG) in the vasodilator response of ESAH on the mesenteric vascular bed (MVB) were also investigated. ESAH treatment induced an important saluretic and antihypertensive response, therefore recovering vascular reactivity in 2K1C plus OVT-rats. This effect was associated with a reduction of oxidative and nitrosative stress with a possible increase in the NO bioavailability. Additionally, a NO and PG-dependent vasodilator effect was observed on the MEV.

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