RESUMO
The effects of gestation on a-actin levels in vascular smooth muscle aortae were studied in 31 fetal sheep, aged 66-144 days (term=150 days). Aortae were collected post-mortem. 2. Aortae, carotid and femoral arteries from two groups of chronically catheterized fetal sheep (110-114 days) were also examined. One group was infused with cortisol (n=6; hydrocortisone sodium succinate, total dose 16.8 mg in 48 h) and the control group received saline (0.15 mol/L, 0.33 mL/h, n=7). 3. Vascular homogenate protein was separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western transfer. a-Actin was identified using a monoclonal mouse anti-a actin antibody and standardized against tissue protein and DNA content. 4. Between 60 and 144 days gestation, there was an exponential increase in the a-actin content of vascular smooth muscle cells from fetal sheep aorta (P<0.0001). a-Actin concentration (densitometry units (U) relative to DNA 260 nm absorbance (Abs)) was significantly (P<0.05) higher in the aortae of cortisol-infused (12,601+/- 2,499 U/Abs) fetal sheep compared with those that were saline-infused (4,514+/-670 U/Abs). a-Actin (relative to DNA absorbance) of carotid and femoral vessels in cortisol-infused animals (20,659+/- 4,812 U/Abs) compared with those that were saline-infused (14,461+/- 2,645 U/Abs) was increased, but the difference was not significant. 5. Therefore, the a-actin concentration of the vascular smooth muscle of the aorta increases throughout gestation. Cortisol treatment is associated with further increases in a-actin concentration in the fetal aorta, indicating that the development of large conduit vessels can be altered by this glucocorticoid.
Assuntos
Actinas/metabolismo , Hidrocortisona/farmacologia , Músculo Liso Vascular/enzimologia , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Western Blotting , DNA/análise , DNA/biossíntese , DNA/genética , Eletroforese em Gel de Poliacrilamida , Feminino , Idade Gestacional , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/embriologia , Gravidez , Proteínas/metabolismo , OvinosRESUMO
The acute and long-term effects of blockade of nitric oxide (NO) production were studied in six chronically catheterised fetal sheep aged from 116 and 118 days; six untreated fetal sheep received injections of saline. Injection of 10 mg (kg maternal body wt)(-1) of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (NOLA) to the fetus, caused an immediate rise in fetal mean arterial pressure (MAP, P < 0.005) and a reflex fall in fetal heart rate (FHR, P < 0.001). Plasma renin concentration (PRC) fell from 8.4 +/- 3.3 to 1.5 +/- 0.3 ng ml(-1) h(-1) (P < 0.001) and was dependent on MAP (P = 0.001). Glomerular filtration rate (GFR) tended to increase, but renal blood flow (RBF) velocity decreased (P < 0.001). Thus filtration fraction (FF) increased (P < 0.025). Urine flow and sodium excretion increased (P < 0.001 for both). Fractional sodium reabsorption decreased (P < 0.05). In fetuses treated with NOLA, arterial pressure was found to affect glomerular haemodynamics and renal tubular handling of sodium. No such relationships were observed in untreated fetuses. The vascular responses to acetylcholine tended to be less (P = 0.07) and the responses to noradrenaline were enhanced in NOLA-treated fetuses. There were no changes in untreated fetuses. Fetuses were then injected twice daily with either 5 mg kg(-1) NOLA or saline for the next 2 days. On the 4th day, injection of 10 mg kg(-1) NOLA did not have any effects on MAP, FHR or renal function. However, the pressor responses to angiotensin II (Ang II) were enhanced (P < 0.005), as was the response to noradrenaline but to a lesser extent. It is concluded that endothelial production of NO maintains normal fetal blood pressure, renal vascular resistance and fetal renal function. When NO production was blocked by repeated injections of NOLA, other vasodilator pathways took over the maintenance of cardiovascular and renal vascular tone. However, alterations in both cardiovascular and renal function were still present. That is, there was increased pressor sensitivity to exogenous Ang II and unmasking of effects of arterial pressure on glomerular and tubular function.
Assuntos
Feto/metabolismo , Hemodinâmica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/embriologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/fisiologia , Angiotensina II/farmacologia , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Feminino , Feto/irrigação sanguínea , Feto/efeitos dos fármacos , Frequência Cardíaca Fetal/efeitos dos fármacos , Testes de Função Renal , Norepinefrina/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Circulação Renal/efeitos dos fármacos , Renina/sangue , Ovinos , Urodinâmica/efeitos dos fármacos , Vasoconstritores/farmacologiaRESUMO
Small size at birth has been associated with increased blood pressure in adult men and women. In rats, isocaloric protein restriction reduces fetal growth and increases systolic blood pressure in adult offspring. Balanced maternal undernutrition in the rat also increases adult blood pressure, but not consistently. The aim of this study was to determine the effect of moderate balanced maternal undernutrition (85% of ad libitum intake from 4 weeks before, and throughout pregnancy) on blood pressure of adult offspring in the guinea pig, a species that is relatively mature at birth. Blood pressure was measured in chronically catheterised offspring of ad libitum fed or feed-restricted mothers, at 3 months of age (young adult). Maternal feed restriction reduced birth weight (-17%) and increased systolic blood pressure (+9%, P < 0.03) in young adult male offspring. In offspring of ad libitum fed and feed-restricted mothers, combined data showed that systolic blood pressure and mean arterial pressure correlated negatively with head width at birth (P = 0.02 and P = 0.04, respectively, n = 28). Systolic blood pressure also correlated negatively with birth weight and the ratio birth weight/birth length, but only in offspring of ad libitum fed mothers (P = 0.04 and P = 0.03, respectively, n = 22). The effect of maternal feed restriction on systolic blood pressure in male offspring was not significant when adjusted for these measures of size at birth. Thus, moderate balanced undernutrition in the guinea pig increases systolic blood pressure in young adult male offspring; however, these effects may be mediated, at least in part, through effects on fetal growth.