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Biomedical subjects

M De Gasparo

Publications and source records attributed to M De Gasparo.

At least 19 recordsLinked to original sources
PubMed1997

Blockade of angiotensin converting enzyme but not of angiotensin AT1 receptors improves glucose tolerance.

This study compared the effect of benazepril, an angiotensin converting enzyme inhibitor to valsartan, an angiotensin AT1 receptor antagonist, on glucose tolerance in the conscious, spontaneously hypertensive rat. Intraperitoneal infusion of benazepril or valsartan at 1, 3 and 10 mg/kg per day produced equivalent dose-related reductions in systolic blood pressure for 12 weeks. Body weight gain during the treatment period was significantly reduced by infusion rates of benazepril. In contrast, only the highest infusion rate of valsartan significantly affected body weight gain. At the end of the 12-week treatment period, neither benazepril nor valsartan significantly affected glucose disposal during intravenous glucose tolerance tests. The insulin response to glucose challenge was unaffected by valsartan whereas following the highest infusion rate of benazepril the plasma levels were significantly reduced. The results demonstrate that benazepril but not valsartan reduces the insulin required to dispose of a glucose load.

Angiotensin Receptor Antagonists↗
PubMed1997

Pharmacokinetics, disposition and biotransformation of [14C]-radiolabelled valsartan in healthy male volunteers after a single oral dose.

1. The disposition of valsartan, a potent angiotensin II receptor antagonist, was investigated in six healthy male volunteers. They each received a single oral dose of 80 mg of a 14C-labelled preparation as a neutral buffered solution. 2. Peak concentrations of radioactivity and valsartan in plasma measured 1 h after dosing showed rapid onset of absorption. The results of this study combined with other available data indicate that at least 51% of the dose was absorbed. 3. Valsartan was the predominant radioactive compound in plasma. Elimination of valsartan and radioactivity was fast and multiexponential. beta-Half-lives of 6 +/- 1 h were observed. In a terminal elimination phase, low radioactivity levels decreased with a half-life of 81 +/- 33 h. A minor, pharmacologically inactive metabolite (valeryl-4-hydroxy-valsartan; M1) was detected in the plasma at time points later than 2 h after dosing, representing approximately 11% of the AUC(24 h) of plasma radioactivity. 4. The bulk of the dose was excreted within 4 days. The total excretion within 7 days amounted to 99 +/- 1% of dose. Faecal excretion was predominant (86 +/- 5% of dose). Valsartan was largely excreted unchanged (81 +/- 5% of the dose in the excreta). The predominant clearance mechanism appeared to be direct elimination via bile. 5. An inactive metabolite, M1, was formed by oxidative biotransformation and accounted for 9 +/- 3% of the dose in the excreta.

Administration, Oral↗
PubMed1997

Effect of interactions between nitric oxide and angiotensin II on pressure diuresis and natriuresis.

The present study examined the effect of an angiotensin II AT1 or AT2 receptor antagonist on the impairment of the pressure diuresis and natriuresis response produced by nitric oxide (NO) synthesis blockade. N omega-nitro-L-arginine methyl ester (L-NAME, 37 nmol.kg-1.min-1) lowered renal blood flow and reduced the slopes of the pressure diuresis and natriuresis responses by 44 and 40%, respectively. Blockade of AT1 receptors with valsartan increased slightly sodium and water excretion at low renal perfusion pressure (RPP). Blockade of AT2 receptors with PD-123319 had no effect on renal function. The administration of valsartan or PD-123319 to rats given L-NAME had no effect on the renal vasoconstriction induced by NO synthesis blockade. In addition, in rats given L-NAME, valsartan elevated baseline excretory values at all RPP studied, but it had no effect on the sensitivity of the pressure diuresis and natriuresis response. However, the administration of PD-123319 to L-NAME-pretreated rats shifted the slopes of the pressure diuresis and natriuresis responses toward control values, indicating that the impairment produced by NO synthesis blockade on pressure diuresis is dependent on the activation of AT2 angiotensin receptors.

Angiotensin II↗
PubMed1996

The renin-angiotensin system in the rabbit eye.

We analyzed the components of the renin-angiotensin system (RAS) in ocular tissues of normal rabbit eyes and compared the results with those measured in rabbit eyes with proliferative vitreoretinopathy and ocular hypertension. Proliferative vitreoretinopathy was induced by injection of human platelets into the vitreous humor, and ocular hypertension was induced by injection of alpha-chymotrypsin into the posterior chamber. Angiotensinogen, renin, angiotensin converting enzyme (ACE), angiotensin II (Ang II), and Ang II receptors were assessed using conventional biochemical techniques. The vascularized tissues of normal eyes contained high renin and ACE activities concomitant with low concentration of angiotensinogen and Ang II. In general, in the ocular humors, the opposite was found. The Ang II receptor density was highest in the uveal tract [range 35-190 fmol/mg protein]. The AT1 receptor subtype predominated [> 80%]. The RAS was only minimally different in the two pathological models except that, in ocular hypertension, the renin activity in the uveal tract was reduced [-50%]. Also, the ratio of AT1 to AT2 receptors changed as compared to control, although the total receptor density remained unaltered. In conclusion, we present evidence for the presence of a complete local RAS in the rabbit eye, which is only marginally affected by the two pathological models studied.

Angiotensin II↗
PubMed1996

Down-regulation of angiotensin AT1 receptor by progesterone in human placenta.

Regulation of the angiotensin AT1 receptor in human placenta is poorly understood. In this study, we analyzed the time course of angiotensin AT1 receptor expression, internalization, and recycling by human trophoblast cells. We also studied the effects of estradiol, progesterone, and chloroquine on regulation of the angiotensin AT1 receptor in 48-h cell culture. The angiotensin II receptor expression increased with the time of incubation, reaching a level at 48 h of culture that was about 120% above the initial value. A large majority of angiotensin II receptors was of the AT1 subtype, as it was completely inhibited by losartan (1 mumol/L). The internalization of [125]angiotensin II binding and the angiotensin AT1 receptor recycling were also time dependent, with t1/2 values of 12 and 21 min, respectively. In human trophoblast cells exposed to progesterone (10 mumol/L) for 48 h, angiotensin AT1 receptor density was decreased by 49%, whereas estradiol (10 mumol/L) or chloroquine (100 mumol/L) treatment was ineffective. In the freshly isolated trophoblast cells initially treated with unlabeled angiotensin II (200 nmol/L) for 30 min, chloroquine was shown to decrease angiotensin AT1 receptor recycling by 73%, whereas estradiol and progesterone had no effect. These findings indicate that progesterone induces a down-regulation of the angiotensin AT1 receptor in human placenta and that the recycling of this receptor can be delayed by chloroquine.

Angiotensin I↗
PubMed1995

Gastric acid secretion after blockade of angiotensin AT1 receptors in the Na(+)-depleted rat.

This study tested the hypothesis that angiotensin II acting through the angiotensin AT1 receptor plays an important role in the control of gastric acid secretion. Basal gastric acid secretion and gastric blood flow were lower in Na(+)-depleted animals, in which the renin-angiotensin system was activated, than in animals maintained on a normal Na+ diet. Intravenous infusion of pentagastrin at 0.6 microgram/kg/min increased gastric acid secretion to a greater extent in normal Na+ than in Na(+)-depleted animals. In addition to stimulating gastric acid secretion, pentagastrin increased gastric blood flow by proportionally the same amount in both normal and low Na+ animals. However, because basal gastric blood flow was considerably reduced in Na(+)-depleted animals, the increase produced by pentagastrin extended only to the levels observed in non-pentagastrin-treated normal Na+ animals. Lower gastric blood flow in response to pentagastrin may explain the smaller increase in gastric acid secretion observed in Na(+)-depleted animals. In Na(+)-depleted animals, the selective angiotensin AT1 receptor antagonist losartan did not affect basal gastric acid secretion or gastric blood flow, suggesting the involvement of mechanisms other than angiotensin II. Following blockade of angiotensin AT1 receptors, pentagastrin significantly increased gastric blood flow in Na(+)-depleted animals to levels observed with infusion of the pentapeptide in normal Na+ animals. The results suggested that the decrease in pentagastrin-stimulated acid secretion in Na(+)-depleted animals is mediated by angiotensin II acting through the angiotensin AT1 receptor, most probably through vascular mechanisms.

Angiotensin I↗
PubMed1995

Improved glucose metabolism following blockade of angiotensin converting enzyme but not angiotensin AT1 receptors.

This study compared the effect of benazepril, an angiotensin converting enzyme inhibitor ([S-(R*,R*)]-3-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5- tetrahydro-2-oxo) to valsartan, an angiotensin AT1 receptor antagonist ((S)-N-valeryl-N-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl-valin e) on glucose metabolism and plasma lipid levels in 11- to 12-week-old conscious spontaneously hypertensive rats. Intraperitoneal infusion of benazepril or valsartan at 1, 3 and 10 mg/kg/day produced dose-related reductions in systolic blood pressure after 12 weeks which were not significantly different from each other. During the infusion, valsartan-treated animals gained weight at the same rate as controls, but all infusion rates of benazepril significantly suppressed normal weight gain, despite both compounds having similar antihypertensive effects. At the end of the 12-week treatment period, benazepril (3 and 10 mg/kg/day) significantly increased glucose disposal but did not significantly affect insulin disposal in insulin/glucose tolerance tests. In contrast, none of the infusion rates of valsartan significantly affected glucose or insulin disposal. Finally, compared to controls benazepril and valsartan were without effect on the fasting basal plasma concentrations of glucose, insulin, triglycerides, total cholesterol and K+. The results demonstrate that angiotensin converting enzyme inhibition and angiotensin AT1 receptor antagonism have similar antihypertensive effects, but express differences on body weight gain and insulin-stimulated glucose disposal in the conscious spontaneously hypertensive rat.

Angiotensin Receptor Antagonists↗
PubMed1995

Angiotensin-II stimulates estradiol secretion from human placental explants through AT1 receptor activation.

A complete renin-angiotensin system has been shown to be present in human placenta, but its physiological role is poorly known. To investigate the implication of this system in the regulation of steroid hormone secretion, we studied the effect of angiotensin-II on the release of estradiol and progesterone from human placental explants. Our experiments showed that angiotensin-II stimulated estradiol secretion from term placental explants in a dose- and time-dependent fashion, although progesterone release was unaffected. Estradiol release induced by angiotensin-II (0.2 mumol/L) was blocked by angiotensin AT1 receptor antagonist losartan in a dose-dependent manner, suggesting the involvement of the AT1 receptor subtype in the process. On the contrary, the angiotensin AT2 receptor antagonist PD123319 (1 mumol/L) or the angiotensin AT2 receptor agonist CGP42112A (1 mumol/L) had no effect. Analysis of the amount of steroid hormones in the placental tissues incubated for 12 h showed that angiotensin-II increased estradiol production by 34% compared with the unstimulated explants, whereas the total levels of the estrogen precursor androstenedione and testosterone were decreased by 30-45% in the presence of the peptide, suggesting a stimulatory effect on the aromatization step. This hypothesis was reinforced by the absence of effect of angiotensin-II on both estradiol and testosterone concentrations in the placental explants pretreated with the aromatase inhibitor 4-hydroxyandrostenedione (25 mumol/L). Progesterone synthesis was not affected by angiotensin-II. The present study indicates that angiotensin-II induces the secretion of estradiol from human placenta through the angiotensin AT1 receptor subtype activation, and this effect seems to be linked to the stimulation of local androgen aromatization.

Angiotensin II↗
PubMed1994

Renal actions of the angiotensin AT2 receptor ligands CGP 42112 and PD 123319 after blockade of the renin-angiotensin system.

The purpose of this study was to investigate whether the selective angiotensin AT2 receptor ligands, CGP 42112B (Nic-Tyr-(N alpha-benzoyloxycarbonyl-Arg)Lys-His-Pro-Ile-OH) and PD 123319 ((s)-1-[[4-(dimethylamino)-3-methyl-phenyl]methyl]-5-(diphenylacetyl+ ++)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]-pyridine-6-carboxylic acid) are agonists at angiotensin receptors influencing blood pressure and renal function in the enalaprilat-treated anesthetized rat. The agonist angiotensin II significantly increased blood pressure and renal vascular resistance. Glomerular filtration rate was unchanged by angiotensin II. Effective renal blood flow decreased significantly in response to angiotensin II leading to a significant increase in filtration fraction. Angiotensin II did not induce significant change in urinary potassium excretion or free water formation but significantly increased both urine volume and urinary sodium excretion. At doses up to 3 orders of magnitude greater than angiotensin II, CGP 42112B also significantly increased blood pressure, filtration fraction, glomerular filtration rate, urine volume and urinary sodium excretion, but did not significantly affect effective renal blood flow or renal vascular resistance. The selective angiotensin AT2 receptor ligand PD 123319 had no significant effects on blood pressure nor any measured parameter of renal function. The changes in blood pressure and renal function produced by angiotensin II and CGP 42112B could be completely blocked by the angiotensin AT1 receptor antagonist losartan. The results therefore only support a role for angiotensin AT1 receptors and not angiotensin AT2 receptors in the control of renal function in the rat and demonstrate that at high doses the angiotensin AT2 selective ligand CGP 42112B behaves as an agonist at angiotensin AT1 receptors.

Angiotensin II↗
PubMed1994

Angiotensin AT2 receptor mediated inhibition of particulate guanylate cyclase: a link with protein tyrosine phosphatase stimulation?

Ever since the identification of two distinct Ang II receptor subtypes, the function of the AT2 receptor has been a subject of debate. As opposed to the AT1 subtype, this receptor does not interact with G-proteins in most cell lines and tissues. We show here that, in intact PC12W cells which express only AT2 receptors, Ang II significantly decreases basal and atrial natriuretic peptide (ANP)-stimulated cGMP concentration. This effect is mimicked by the AT2 selective agonist CGP 42112, and is not prevented by the AT1 selective antagonist losartan, indicating that this is an AT2 receptor mediated response. The lack of effect of the phosphodiesterase (PDE) inhibitor IBMX shows that this mechanism does not involve PDE stimulation. This is confirmed by the finding that neither Ang II or CGP 42112 affect the Ca++/calmodulin dependent cGMP PDE activity. Furthermore Ang II and CGP 42112 have no effect on nitroprusside-stimulated cGMP levels in these cells, thus ruling out interactions between the AT2 receptor and soluble guanylate cyclase. These data indicate that the AT2 receptor mediated decrease of cGMP is due to the selective inhibition of particulate guanylate cyclase (pGC) activity. In an accompanying paper we report that interaction of Ang II with the AT2 receptor in the same cells results in the stimulation of phosphotyrosine phosphatase (PTPase) activity. Interestingly, the PTPase inhibitors sodium orthovanadate and phenylarsine oxyde, but not the Ser/Thr phosphatase inhibitor okadiac acid, inhibitthe Ang II and CGP 42112 induced decreases in cellular cGMP concentration. These findings suggest that stimulation of PTPase activity may be involved in the regulation of pGC activity via AT2 receptors.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Angiotensin II stimulates protein tyrosine phosphatase activity through a G-protein independent mechanism.

Most of angiotensin II's (Ang II) documented effects have been attributed to the interaction of this peptide with a G-protein coupled receptor termed AT1. The role and the signalling mechanisms of the more recently characterized AT2 receptor, which does not appear to interact with G-proteins, are however still unclear. We report here that this receptor mediates the rapid dephosphorylation of tyrosine residues of specific proteins in the 60 to 150 KDa range in PC12W cells which express only AT2 receptors. We further characterized this phosphatase activity using the synthetic substrate para-nitrophenyl phosphate. Dephosphorylation of this substrate in response to Ang II is not affected by Ser/Thr phosphatase inhibitors, but is completely prevented by the protein tyrosine phosphatase (PTPase) inhibitor sodium orthovanadate. This effect is mimicked by the AT2 selective agonist CGP42112 and is not affected by the AT1 antagonist losartan, In contrast to the recently reported PTPase stimulation by somatostatin and dopamine, PTPase stimulation by Ang II is not affected by the guanyl nucleotides GTP gamma S and GDP beta S. Moreover, depletion of solubilized membrane preparations from G-proteins by lectin affinity chromatography does not alter Ang II stimulation of the measured PTPase activity. These findings indicate that Ang II stimulates a PTPase activity through AT2 receptors via G-protein independent pathways. This signalling mechanism may be involved in AT2 receptor mediated actions of Ang II such as particulate guanylate cyclase inhibition, modulation of T-type Ca++ channels and regulation of cell proliferation and differentiation.

Angiotensin II↗
PubMed1993

Renal actions of the selective angiotensin AT2 receptor ligands CGP 42112B and PD 123319 in the sodium-depleted rat.

The purpose of this study was to investigate the renal actions of the new selective angiotensin AT2 receptor ligands, CGP 42112B and PD 123319, in comparison to those of the AT1 receptor antagonist losartan, in the sodium-depleted, anesthetized rat. Losartan (1, 3 and 10 mg/kg i.v.) produced a dose-dependent decrease in blood pressure and renal vascular resistance that was statistically significant. Effective renal blood flow tended to increase in response to all doses of losartan while glomerular filtration rate either did not change or decreased, leading to a significant fall in filtration fraction. Losartan did not induce significant changes in urine volume, urinary sodium excretion, urinary potassium excretion or free water formation. The selective AT2 receptor ligand CGP 42112B at infusion rates of 1-100 micrograms/kg per min i.v. had no significant effect on blood pressure or any measured parameter of renal function. However, when infused at 1000 micrograms/kg per min i.v., CGP 42112B did not affect blood pressure, but significantly increased effective renal blood flow, glomerular filtration rate, urinary sodium excretion, urinary potassium excretion and free water formation, while significantly decreasing renal vascular resistance. The selective AT2 receptor ligand PD 123319 at infusion rates between 1 and 100 micrograms/kg per min i.v. also had no significant effect on blood pressure or on any measured parameter of renal function. However, at an infusion rate of 1000 micrograms/kg per min i.v., PD 123319 tended to increase renal vascular resistance, urinary sodium excretion, urinary potassium excretion and free water formation, and to decrease effective renal blood flow, although none of these changes reached a level of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

[Distribution of the concentrations of angiotensin II (A II), A II receptors, hPL, prolactin, and steroids in human fetal membranes].

By analyzing human trophoblastic tissues at the full term of pregnancy, this study shows the highest levels of angiotensin-II (729 +/- 111 and 602 +/- 105 pg/g of tissue), angiotensin-II receptors (295 +/- 30 and 250 +/- 32 fmol/mg proteins), human placental lactogen (973 +/- 154 and 680 +/- 28 micrograms/g) and progesterone (1,501 +/- 193 and 1,070 +/- 151 ng/g) in chorionic villi and in placental basal plate respectively. Tissue values of angiotensin-II, hPL and Progesterone were 4 times superior to those obtained in amniotic fluid and in umbilical and maternal blood. Estradiol values in chorionic villi were similar to those in placental basal plate, in chorionic plate and in chorion, but significantly higher (p less than 0,001) than in amnion, amniotic fluid and in umbilical and maternal blood. The concentrations of prolactin in chorion were 3 times superior than those found in amnion, in placental tissue, in amniotic fluid and in umbilical and maternal blood. A positive correlation was observed between Angiotensin-II and its receptors and also with hPL, P4/hPL ratio and E2/P4 ratio. Thus, angiotensin-II could play an important role in the physiology of pregnancy, due to its vasopressive action and due to its interactions with other peptides and chorio-placental steroids.

Angiotensin II↗
PubMed1991

[Study of the fetal and maternal renin-angiotensin system and chorio-placental steroids in the guinea pig].

1.) Total renin, active renin, prorenin, angiotensin II, estradiol and progesterone were measured in maternal, placental and fetal blood and in trophoblastic and uterine tissues of the guinea pig. Furthermore, membrane angiotensin II receptors were measured in trophoblastic tissues. 2.) Blood and tissue concentrations of total renin, active renin, angiotensin II and steroids are shown to increase with gestational age. At the full term of pregnancy (70th post-coital day), tissue concentrations of total renin in chorion (23,900 +/- 2,752 ng/g of tissue/h), maternal placenta (14,210 +/- 1,131), fetal placenta (12,475 +/- 927) and uterus (7,677 +/- 798) are 100 time higher than those observed in placental, fetal and maternal blood. Distribution of blood and tissue prorenin (inactive renin) is similar to that found for total renin. Active renin/Total renin ratio reaches 1% in uterine, placental and chorion tissues and 9.3 +/- 1.0% in maternal, placental and fetal blood. 3.) Angiotensin II levels in systemic maternal blood (690 +/- 99 pg/ml) and in uterine blood (467 +/- 84) are higher than those found in placental blood (266 +/- 39) and in different trophoblastic tissues (between 200 and 400 pg/g). Angiotensin II receptor concentrations are highest in chorion. 4.) Regarding the steroid hormones, it is noted that placental and maternal blood contain more progesterone than trophoblastic tissues. The highest concentrations of estradiol are found in chorion tissue and uterine blood. 5.) A positive correlation is observed between angiotensin II and estradiol in uterine blood (r = 0.69, P less than 0.01) and in chorion (r = 0.71, P less than 0.01). These findings indicate that angiotensin II and estradiol could, by their interactions, play an important role in the physiology of pregnancy.

Animals↗
PubMed1989

Down-regulation of protein kinase C potentiates angiotensin II-stimulated polyphosphoinositide hydrolysis in vascular smooth-muscle cells.

In smooth-muscle cells (SMC) isolated from rat aorta, angiotensin II stimulates a phospholipase C with subsequent formation of inositol trisphosphate (InsP3). Short-term (10 min) pretreatment of SMC with 12-O-tetradecanoylphorbol 13-acetate (TPA; 100 nM) decreases the angiotensin II-induced InsP3 formation. However, this inhibition is not observed after incubating the cells for 2 h with TPA. Longer-term pretreatments even lead to an enhanced generation of InsP3. This increased response to angiotensin II occurs without a significant change in the receptor number or Kd value of angiotensin II binding to the cells. The biologically inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate was without effect on angiotensin II-stimulated InsP3 generation, irrespective of the time of preincubation. In parallel with this potentiation of angiotensin II-induced generation of InsP3 by TPA, a down-regulation of protein kinase C activity is observed. A 24 h pretreatment of SMC with TPA decreases protein kinase C activity to less than 10% of that of control cells. Longer-term pretreatment also increases the angiotensin II-induced release of Ca2+ and delays the decay of the transient Ca2+ increase. All these data suggest that protein kinase C exerts a negative feedback control on angiotensin II-stimulated polyphosphoinositide turnover, and that protein kinase C is an important factor in limiting the production of InsP3 in stimulated cells.

Angiotensin II↗
PubMed1989

Hemodynamic and biochemical consequences of renin inhibition by infusion of CGP 38560A in normal volunteers.

Hemodynamic and biochemical effects of the new renin inhibitor CGP 38560A (molecular weight 826) were tested in 15 healthy volunteers after a single-blind, randomized, placebo-controlled protocol. At a 2-week interval, groups of five subjects received a 30-minute infusion of either 5% dextrose or CGP 38560A 50, 125, or 250 micrograms/kg. Blood pressure, heart rate, plasma renin activity, active and total renin, angiotensin-(1-8)octapeptide (angiotensin II), and aldosterone were sequentially measured up to 3 hours from the onset of the infusion. There was no consistent change in blood pressure or heart rate. Plasma renin activity and angiotensin II decreased dose dependently, and peak suppression was observed at the end of the infusion of CGP 38560A and after the 250-micrograms/kg dose. Plasma renin activity fell from 1.0 +/- 0.19 (mean +/- SEM) to less than 0.05 ng/ml/hr in all five subjects (p less than 0.001), and angiotensin II fell from 7.7 +/- 1.2 to 2.6 +/- 0.9 femtomole/ml (p less than 0.01). Active renin rose fourfold from 24 +/- 1.9 to 98 +/- 14 pg/ml (p less than 0.001) at the end of the infusion of the high dose. Plasma angiotensin II returned toward its initial values much faster than plasma renin activity and active renin. In conclusion, CGP 38560A was well tolerated. It induced a dose-dependent decrease in angiotensin II and plasma renin activity and a long-lasting and dose-dependent rise in active renin. The doses used did not reduce plasma angiotensin II maximally despite reduction of plasma renin activity to unmeasurable levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

The autonomic nervous system and perinatal metabolism.

The development of the autonomic nervous system in relation to perinatal metabolism is reviewed with particular attention given to the adipocyte, hepatocyte and the A and B cells of the islets of Langerhans. Adrenergic receptors develop in the B cell independently of normal innervation and by the time of birth, in most species studied, the pancreas, liver and adipose tissue respond appropriately to autonomic signals. Birth is associated with a huge surge in circulating catecholamines which is probably responsible for the early postnatal rise in free fatty acids and glucagon concentrations in plasma. beta-Blocking drugs such as propranolol have an adverse effect on fetal growth and neonatal metabolism, being responsible for hypoglycemia and for impairing the thermogenic response to cold exposure. beta-Mimetic drugs are commonly used to prevent premature labour and may help the fetus in other ways, for example, by improving the placental blood supply and the delivery of nutrients by increasing maternal fat and carbohydrate mobilization.

Adipose Tissue↗