Treatment of newborn rats with a VEGF receptor inhibitor  causes pulmonary hypertension and abnormal lung structure

To determine whether disruption of vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) signaling in the newborn has long-term effects on lung structure and function, we injected 1-day-old newborn rat pups with a single dose of Su-5416, a VEGFR inhibitor, or vehicle (controls). Lungs from infant (3-wk-old) and adult (3- to 4-mo-old) rats treated with Su-5416 as newborns showed reductions in arterial density (82 and 31%, respectively) and alveolar counts (45 and 29%) compared with controls. Neonatal treatment with Su-5416 increased right ventricle weight to body wt ratios (4.2-fold and 2.0-fold) and pulmonary arterial wall thickness measurements (2.7-fold and 1.6-fold) in infant and adult rats, respectively, indicating marked pulmonary hypertension. We conclude that treatment of newborn rats with the VEGFR inhibitor Su-5416 impaired pulmonary vascular growth and postnatal alveolarization and caused pulmonary hypertension and that these effects were long term, persisting well into adulthood.

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Prenatal and perinatal factors influencing nociception, addiction and behavior during ontogenetic development

Physiological Research ◽

10.33549/physiolres.931602 ◽

2008 ◽

pp. S79-S88

Author(s):

R Rokyta ◽

A Yamamotová ◽

R Šlamberová ◽

M Franěk ◽

Š Vaculín ◽

...

Keyword(s):

Neuropathic Pain ◽

Postnatal Period ◽

Long Term Effects ◽

Perinatal Factors ◽

Adult Rats ◽

Factors Affecting ◽

Dorsal Rhizotomy ◽

Rat Pups ◽

Factors Influencing

This review, which summarizes our findings concerning the long-term effects of pre-, peri- and postnatal factors affecting development, nociception and sensorimotor functions, focuses on three areas: 1) perinatal factors influencing nociception in adult rats were examined in rats with hippocampal lesions, after the administration of stress influencing and psychostimulant drugs (dexamethasone, indomethacine and methamphetamine); 2) the effect of pre- and early postnatal methamphetamine administration was shown to impair the development of sensorimotor functions tested in rat pups throughout the preweaning period; 3) the effect of extensive dorsal rhizotomy of the brachial plexus during the early postnatal period was studied with respect to neuropathic pain development and sensorimotor functions. The present study indicates that prenatal or neonatal stress, as well as various drugs, may disturb the development of the nociceptive system and cause long-term behavioral changes persisting to adulthood and that some types of neuropathic pain cannot be induced during the first two postnatal weeks at all. A mature nervous system is required for the development of the described pathological behaviors.

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P3264 Milrinone versus dobutamine as continuous outpatient parenteral inotropic therapy in pre-transplant chronic heart failure patients with reversible pulmonary hypertension: long-term effects

European Heart Journal ◽

10.1016/s0195-668x(03)95890-8 ◽

2003 ◽

Vol 24 (5) ◽

pp. 617

Author(s):

G KARAVOLIAS

Keyword(s):

Heart Failure ◽

Pulmonary Hypertension ◽

Chronic Heart Failure ◽

Long Term Effects ◽

Inotropic Therapy ◽

Heart Failure Patients

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Long-term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA-nano Artificial Red Blood Cells

Artificial Cells Blood Substitutes and Biotechnology ◽

10.1080/10731190802554224 ◽

2008 ◽

Vol 36 (6) ◽

pp. 513-524 ◽

Cited By ~ 15

Author(s):

Zun Chang Liu ◽

Thomas M.S. Chang

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Long Term Effects ◽

And Function

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Lung Structure And Function Relation In Elastase-Treated Rats: A Long-Term Follow Up Study

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6405 ◽

2012 ◽

Author(s):

Margit V. Szabari ◽

Jozsef Tolnai ◽

Balazs Maar ◽

Harikrishnan Parameswaran ◽

Elizabeth Bartolak-Suki ◽

...

Keyword(s):

Structure And Function ◽

Follow Up Study ◽

Lung Structure ◽

Long Term Follow Up ◽

And Function ◽

Function Relation

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Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

Journal of Endocrinology ◽

10.1677/joe.0.1230083 ◽

1989 ◽

Vol 123 (1) ◽

pp. 83-91 ◽

Cited By ~ 10

Author(s):

K.-L. Kolho ◽

I. Huhtaniemi

Keyword(s):

Body Weight ◽

Gnrh Agonist ◽

Gnrh Antagonist ◽

Long Term Effects ◽

Adult Rats ◽

Releasing Hormone ◽

Serum Lh ◽

Accessory Sex Organs ◽

Gonadotrophin Releasing Hormone

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91

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Abstract P138: Long-term Effects Of Severe Caloric Restriction To The Heart Function

Hypertension ◽

10.1161/hyp.78.suppl_1.p138 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Aline M De Souza ◽

Jonathas Almeida ◽

Nataliia Shults ◽

Hong Ji ◽

Kathryn Sandberg

Keyword(s):

Cardiovascular Disease ◽

Caloric Restriction ◽

Heart Function ◽

Left Ventricular ◽

Structure And Function ◽

Long Term Effects ◽

Isolated Hearts ◽

Ad Libitum ◽

And Function

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.

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