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Australia↗
Biomedical subjects
Warwick P Anderson
Publications and source records attributed to Warwick P Anderson.
Renal structural and functional repair in a mouse model of reversal of ureteral obstruction.
The end point of immune and nonimmune renal injury typically involves glomerular and tubulointerstitial fibrosis. Although numerous studies have focused on the events that lead to renal fibrosis, less is known about the mechanisms that promote cellular repair and tissue remodeling. Described is a model of renal injury and repair after the reversal of unilateral ureteral obstruction (UUO) in male C57bl/6J mice. Male mice (20 to 25 g) underwent 10 d of UUO with or without 1, 2, 4, or 6 wk of reversal of UUO (R-UUO). UUO resulted in cortical tubular cell atrophy and tubular dilation in conjunction with an almost complete ablation of the outer medulla. This was associated with interstitial macrophage infiltration; increased hydroxyproline content; and upregulated type I, III, IV, and V collagen expression. The volume density of kidney occupied by renal tubules that exhibited a brush border was measured as an assessment of the degree of repair after R-UUO. After 6 wk of R-UUO, there was an increase in the area of kidney occupied by repaired tubules (83.7 +/- 5.9%), compared with 10 d UUO kidneys (32.6 +/- 7.3%). This coincided with reduced macrophage numbers, decreased hydroxyproline content, and reduced collagen accumulation and interstitial matrix expansion, compared with obstructed kidneys from UUO mice. GFR in the 6-wk R-UUO kidneys was restored to 43 to 88% of the GFR in the contralateral unobstructed kidneys. This study describes the regenerative potential of the kidney after the established interstitial matrix expansion and medullary ablation associated with UUO in the adult mouse.
Analysis of Variance↗
Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow.
The aim of the current study was to determine whether renal medullary oxygenation is independent of the level of cortical blood flow by testing responses to stimuli that selectively reduce blood flow in either the cortex or medulla. In anesthetized rabbits, renal arterial infusion of [Phe(2),Ile(3),Orn(8)]-vasopressin selectively reduced medullary perfusion and Po(2) (-54 +/- 24 and -50 +/- 10%, respectively) but did not significantly affect cortical perfusion or tissue oxygenation. In contrast, stimulation of the renal nerves resulted in renal cortical ischemia with reductions in total renal blood flow (-76 +/- 3% at 4 Hz), cortical perfusion (-57 +/- 17%), and cortical Po(2) (-44 +/- 12%). Medullary tissue Po(2) was reduced by -70 +/- 5% at 4 Hz, despite medullary perfusion being unaffected and distal tubular sodium reabsorption being reduced (by -83.3 +/- 1.2% from baseline). In anesthetized rats, in which renal perfusion pressure was maintained with an aortic constrictor, intravenous infusion of ANG II (0.5-5 microg. kg(-1).min(-1)) dose dependently reduced cortical perfusion (up to -65 +/- 3%; P < 0.001) and cortical Po(2) (up to -57 +/- 4%; P < 0.05). However, medullary perfusion was only significantly reduced at the highest dose (5 microg. kg(-1).min(-1); by 29 +/- 6%). Medullary perfusion was not reduced by 1 microg. kg(-1).min(-1) ANG II, but medullary Po(2) was significantly reduced (-12 +/- 4%). Thus, although cortical and medullary blood flow may be independently regulated, medullary oxygenation may be compromised during moderate to severe cortical ischemia even when medullary blood flow is maintained.
Animals↗
Paradoxical structural effects in the unilaterally denervated spontaneously hypertensive rat kidney.
OBJECTIVE: To determine the effects of chronic denervation on renal vascular structure and function in young adult spontaneously hypertensive rats (SHRs). DESIGN: Unilateral renal denervation (SHRUDx) or sham-operation (SHRS) was performed in SHRs at 6 weeks of age. At 10 weeks, rats were allocated to one of three procedures designed to examine renal vascular structure and function. A further group underwent bilateral renal denervation. METHODS: In SHRUDx or SHRS groups, either the kidneys were perfusion-fixed for stereological estimates of artery wall and lumen dimensions or for vascular casting to determine arteriole lumen diameters, or the rats were anaesthetized for estimation of glomerular capillary pressure. RESULTS: Chronic unilateral renal denervation had no significant effect on the development of hypertension between 6 and 10 weeks of age, as previously reported, but resulted in luminal narrowing of the interlobular artery (denervated group 52 +/- 2 mum, sham-operated group 64 +/- 1 mum; P < 0.01 for interaction between strain and treatment), without alterations in interlobular or arcuate artery wall dimensions. There were no significant effects on either afferent or efferent arteriole lumen diameters. Estimated glomerular capillary pressure was significantly lower in the denervated kidneys of SHRUDx (47 +/- 1 mmHg) compared with kidneys of the SHRS (50 +/- 1 mmHg; P < 0.04). Mean arterial pressure was approximately 12 mmHg lower in the bilaterally denervated SHRs than in the sham-operated SHRs. CONCLUSIONS: Although bilateral denervation attenuated the development of hypertension in SHRs, unilateral denervation did not, indicating that one neurally intact kidney was sufficient to drive the normal development of SHR hypertension, but only with apparent prohypertensive compensatory changes in the denervated kidney.
Animals↗
Role of endothelin in noradrenaline-induced hypertension in rats.
OBJECTIVE: To investigate the role of endothelin in noradrenaline-induced hypertension in rats. DESIGN: The dose-response relationship of chronic noradrenaline infusion on arterial pressure was characterized to identify a dose that would produce sustained hypertension, and the effect of combined endothelin ETA and ETB receptor blockade (TAK-044) on the response to this dose was then examined. METHODS AND RESULTS: Noradrenaline (or vehicle) was infused intravenously at 1 (subpressor acutely), 24 or 48 microg/kg per h (acute pressor response of 9 +/- 1 and 11 +/- 1 mmHg, respectively) for a 14-day infusion, and blood pressure was measured by radiotelemetry. Noradrenaline infusion at 1 microg/kg per h did not produce a 'slow pressor' rise in blood pressure. During noradrenaline infusions at 24 and 48 microg/kg per h, mean arterial pressure peaked initially on days 2-3 (+10 +/- 1 and 14 +/- 2 mmHg, respectively; P < 0.01), fell towards basal levels after day 3, and then began to rise again at days 5-6 only with 48 microg/kg per h, being 10 +/- 1 mmHg above control levels at days 13-14 (P < 0.05). TAK-044 treatment did not alter the magnitude of the initial (13 +/- 1 mmHg) or eventual (12 +/- 2 mmHg) rise in blood pressure achieved in response to 14 days' infusion of noradrenaline at 48 microg/kg per h, but abolished the transient fall. CONCLUSION: Chronic noradrenaline infusion at acutely pressor doses leads either to a transient blood pressure elevation at a moderate dose, or to a triphasic but sustained hypertension at a higher dose, with a temporary escape from the hypertension apparently mediated by endothelin.
Animals↗
Optimizing microarray in experimental hypertension.
BACKGROUND: Genetic noise between outbred animals can potentially be a major confounder in the use of microarray technology for gene expression profiling. The study of paired organs from the same animal offers an alternative approach (e.g., for studies of the kidney in experimental hypertension). The present study was undertaken to determine the level of genetic noise between outbred adult Sprague-Dawley (SD) rats, and to determine the effects of unilateral nephrectomy on changes in gene expression as a basis for the design of microarray studies in experimental hypertension. METHODS: Male SD rats (approximately 130 g) were acclimatized before measurement of tail-cuff systolic blood pressure (SBP) for 6 control days and 4 days of saline treatment. Left kidney nephrectomy was performed, and the tissue snap-frozen in liquid nitrogen for subsequent RNA extraction. Two weeks later, SBP was measured over 4 control and 8 saline treatment days, and the remaining right kidney removed and frozen. Total RNA purification, preparation of cRNA, hybridization, and scanning of the Rat U34A Affymetrix arrays were performed, and data analyzed using MAS5 software Affymetrix Suite (v5), Bioconductor, as well as statistical methods motivated by relevant simulations. RESULTS: Gene expression profiles in the left control kidney were extremely consistent across animals. The expression profiles of pairs of kidneys from the same animal were, however, more similar than those of kidneys from different animals. Nephrectomy had little effect on the gene expression profiles in the time frame examined. CONCLUSION: Despite the outbred nature of the rats used in this study, they are useful for gene expression profiling comparisons. The use of paired organs from an individual animal ensures even further genetic identity, allowing determination of genes modified by the treatment of interest.
Animals↗
Predominant postglomerular vascular resistance response to reflex renal sympathetic nerve activation during ANG II clamp in rabbits.
We have shown previously that a moderate reflex increase in renal sympathetic nerve activity (RSNA) elevated glomerular capillary pressure, whereas a more severe increase in RSNA decreased glomerular capillary pressure. This suggested that the nerves innervating the glomerular afferent and efferent arterioles could be selectively activated, allowing differential control of glomerular capillary pressure. A caveat to this conclusion was that intrarenal actions of neurally stimulated ANG II might have contributed to the increase in postglomerular resistance. This has now been investigated. Anesthetized rabbits were prepared for renal micropuncture and RSNA recording. One group (ANG II clamp) received an infusion of an angiotensin-converting enzyme inhibitor (enalaprilat, 2 mg/kg bolus plus 2 mg.kg(-1).h(-1)) plus ANG II ( approximately 20 ng.kg(-1).min(-1)), the other vehicle. Measurements were made before (room air) and during 14% O(2). Renal blood flow decreased less during ANG II clamp compared with vehicle [9 +/- 1% vs. 20 +/- 4%, interaction term (P(GT)) < 0.05], despite a similar increase in RSNA in response to 14% O(2) in the two groups. Arterial pressure and glomerular filtration rate were unaffected by 14% O(2) in both groups. Glomerular capillary pressure increased from 33 +/- 1 to 37 +/- 1 mmHg during ANG II clamp and from 33 +/- 2 to 35 +/- 1 mmHg in the vehicle group before and during 14% O(2), respectively (P(GT) < 0.05). During ANG II clamp, postglomerular vascular resistance was still increased in response to RSNA during 14% O(2), demonstrating that the action of the renal nerves on the postglomerular vasculature was independent of the renin-angiotensin system. This further supports our hypothesis that increases in RSNA can selectively control pre- and postglomerular vascular resistance and therefore glomerular ultrafiltration.
Angiotensin II↗
Pre-weaning carvedilol treatment in spontaneously hypertensive rats.
Hypertension in spontaneously hypertensive rats (SHR) has been permanently abolished by aggressive treatment regimens targeted against the sympathetic nervous system and adrenal medulla, initiated during the pre-weaning period (guanethidine and nerve growth factor antiserum combined with either adrenal demedullation or prazosin treatment). To investigate the components of the sympatho-adrenal system involved, we treated pre-weaning SHR with the combined alpha(1)- and beta-adrenoceptor antagonist carvedilol (60 mg/kg/day s.c.; postnatal days 1-21). Carvedilol treatment significantly blocked adrenoceptors during the treatment period, delayed development (eye opening), reduced growth, and reduced arterial pressure and heart rate. However, there was only modest attenuation of the subsequent development of hypertension at 10 weeks of age (mean arterial pressure 129.5+/-1.8 versus 136.1+/-1.6 mm Hg in vehicle-treated littermates; P<0.05). Thus pre-weaning carvedilol treatment slightly but significantly attenuated the development of SHR hypertension at 10 weeks, suggesting that the profound antihypertensive effects of pre-weaning sympatho-adrenal ablation are attributable to factors other than alpha(1)- and beta-adrenoceptor-mediated effects of catecholamines during this period.
Adrenergic alpha-Antagonists↗
Selective increase in renal arcuate innervation density and neurogenic constriction in chronic angiotensin II-infused rats.
This study investigated the effects of angiotensin II "slow pressor" hypertension on structure and function of nerves supplying the renal vasculature. Low-dose angiotensin II (10 ng/kg per minute, initially sub-pressor) or saline vehicle was infused intravenously for 21 days in rats, and the effects were compared in renal and mesenteric arteries. Mean arterial pressure averaged 12+/-2 mm Hg higher than in vehicle-infused rats at 21 days. Using electron microscopy, the innervation density of renal arcuate, but not mesenteric arteries of equivalent size, was significantly higher in angiotensin II-infused than in vehicle-infused rats. Functional testing on a pressure myograph revealed that constrictions evoked by nerve stimulation in arcuate arteries were 2.3+/-0.7-fold greater in vessels from angiotensin II-infused compared with vehicle-infused rats (P<0.0001), whereas there was no significant difference in nerve-induced constrictions in mesenteric arteries. Sensitivity to and maximum amplitude of constrictions evoked by phenylephrine were not different in renal or mesenteric arteries between groups, suggesting that the increased neurally evoked constriction in renal arcuate arteries was not caused by postsynaptic changes. Endothelium-dependent vasorelaxation and the vessel wall physical properties were not different between the two groups in either artery. Thus, angiotensin II infusion appeared to evoke renal-specific increases in vessel innervation and increased vasoconstriction to nerve stimulation. These changes appear early and occur before changes in renal endothelial function are apparent. Thus, "slow pressor" angiotensin II hypertension is associated with increased renal innervation, compatible with a pathogenetic role.
Angiotensin II↗
Effects of early carvedilol treatment and withdrawal on the development of hypertension and renal vascular narrowing.
BACKGROUND: The aims of this study were to examine whether combined blockade of alpha(1) and beta-adrenoceptors with carvedilol postweaning affected the development of hypertension and renal vascular narrowing in spontaneously hypertensive rats (SHR), and whether these effects on pressure and renal vascular changes persisted after treatment withdrawal. METHODS: From 4 to 12 weeks of age male SHR were administered carvedilol in rat chow at 1.2 mg/g chow (low-dose) or 2.4 mg/g chow (high-dose), or were given normal chow. At 12 weeks of age, rats from each group either underwent experimentation or had treatment withdrawn and were studied at 20 weeks. On the experimental day, conscious mean arterial pressure (MAP) was measured and, as a functional test of renal vessel lumen characteristics, pressure-flow and pressure-glomerular filtration rate (pressure-GFR) relationships were determined in the maximally dilated kidney. RESULTS: At 12 weeks of age, SHR on low and high-dose carvedilol had significantly lower MAP than that of untreated SHR (137 +/- 3, 134 +/- 1, 152 +/- 2 mm Hg, respectively; P <.001). The SHR treated with high-dose (but not low-dose) carvedilol demonstrated a steeper renal pressure-flow relationship (P <.001), and a leftward shifted (P <.01) and steeper (P <.001) pressure-GFR relationship compared with control SHR. Eight weeks after carvedilol withdrawal, there were no significant differences in MAP, pressure-flow, or pressure-GFR relationships between groups. CONCLUSIONS: These results suggest that postweaning alpha(1) and beta-adrenoceptor blockade with high-dose carvedilol attenuated the development of hypertension and led to a preferential reduction in preglomerular resistance (increased lumen dimensions) independent of the effects on MAP. However, treatment of SHR from 4 to 12 weeks of age with high-dose carvedilol did not lead to persistent, long-term effects on arterial pressure or renal vascular narrowing after treatment withdrawal.
Adrenergic beta-Antagonists↗
Mechanisms underlying the differential control of blood flow in the renal medulla and cortex.
There is much evidence that the medullary circulation plays a key role in regulating renal salt and water handling and, accordingly, the long-term level of arterial pressure. It has also recently become clear that various regulatory factors can affect medullary blood flow (MBF) differently from cortical blood flow (CBF). It appears likely that the influence of hormonal and neural factors on the control of arterial pressure is mediated partly through their impact on MBF. In this review, we focus on the mechanisms underlying the differential control of MBF and CBF, particularly the relative insensitivity of MBF to vasoconstrictors such as angiotensin II, endothelin-1 and the sympathetic nerves. The vascular architecture of the kidney appears to be arranged in a way that protects the renal medulla from ischaemic insults, with juxtamedullary arterioles, the source of MBF, having larger calibre than their counterparts in other kidney regions. Indeed, recent studies using vascular casting methodology suggest that juxtamedullary glomerular arterioles are not the chief regulators of MBF, which is consistent with the idea that outer medullary descending vasa recta play a key role in MBF control. Release of vasoactive paracrine factors such as nitric oxide and various eicosanoids from the vascular endothelium, and probably also from the tubular epithelium, appear to differentially modulate responses of MBF and CBF to hormonal and neural factors. The prevailing intrarenal hormonal milieu and existing haemodynamic conditions also appear to strongly modulate these responses, indicating that multiple control systems interact to regulate regional kidney blood flow at an integrative level.
Animals↗
Adult rabbit offspring of mothers with secondary hypertension have increased blood pressure.
Preexisting chronic hypertension complicates up to 5% of pregnancies and is associated with an increased risk of low-birth-weight babies. Studies suggest that an adverse intrauterine environment leading to low birth weight is linked to an increased risk of cardiovascular disease, including hypertension, in the adult. In this study, the blood pressure of offspring from mothers with hypertension were followed up into adulthood. Two-kidney, 1-wrapped hypertension was induced in 7 female rabbits; 5 other rabbits underwent sham surgery. Four weeks later, rabbits were mated, at which time mean arterial pressure was 118+/-3 and 87+/-5 mm Hg in the hypertensive and sham groups, respectively (P<0.001). The blood pressure of 30-week-old females was 89+/-2 mm Hg in the offspring of hypertensive (n=14) and 79+/-1 mm Hg in the offspring of normotensive (n=13) mothers (P<0.005). Also, plasma renin activity was significantly lower in the female offspring of hypertensive mothers at 10 weeks of age (P<0.05), suggesting that development of the renin-angiotensin system was altered. In contrast, male offspring from hypertensive and normotensive mothers had similar mean arterial pressure and plasma renin activity. In conclusion, maternal secondary hypertension can "program" hypertension in female adult offspring. The results also suggest that there are gender-specific differences in sensitivity to altered in utero environmental influences.
Animals↗
Effects of preweaning doxazosin treatment on adult pressure in the spontaneously hypertensive rat.
1. The neonatal/preweaning period appears to represent a critical period of involvement of the sympathetic nervous system in the development of hypertension in spontaneously hypertensive rats (SHR). 2. We tested whether alpha1-adrenoceptor-mediated effects during the preweaning period are involved in the development of hypertension in the adult SHR. 3. Male SHR were treated with the alpha1-adrenoceptor antagonist doxazosin (10 mg/kg per day, s.c.) from postnatal day 1 to 21 inclusive. Direct conscious blood pressure and heart rate were measured via the caudal artery at 12 weeks of age. 4. Preweaning treatment with doxazosin had no significant effect on mean arterial blood pressure or heart rate in male SHR at 12 weeks of age. 5. These findings do not support the involvement of alpha1-adrenoceptor-mediated effects during the preweaning period in the development of hypertension in adult SHR.
Adrenergic alpha-Antagonists↗
Evidence for renal vascular remodeling in angiotensin II-induced hypertension.
OBJECTIVES: To determine whether 'slow pressor' hypertension from systemic angiotensin (Ang II) infusion was associated with renal vascular structural remodeling of the renal resistance vessels and glomerulus. METHODS: Ang II (4.5-10 ng/kg per min) or vehicle was infused for 10 days. Renal resistance vascular lumen changes were assessed at 10 days as changes in renal pressure flow and pressure-glomerular filtration rate (GFR) and pressure-Na+ excretion in maximally dilated, isotonically perfused kidneys. RESULTS: Low-dose, initially subpressor Ang II infusion for 10 days increased conscious arterial pressure by 27 mmHg compared to vehicle-infused rats (140 +/- 7 and 113 +/- 2 mmHg, respectively). There was no change in the pressure-flow relationship but the slope of the pressure-GFR relationship was reduced in the rats treated with Ang II. These changes are consistent with equal and opposite pre-and post-glomerular effects (i.e., increased pre-glomerular vessel resistance and reduced post-glomerular vessel resistance) and reduced glomerular ultrafiltration coefficient. There was also a significant reduction in pressure-dependent Na+ excretion. CONCLUSIONS: Slow pressor Ang II-induced hypertension was associated with apparent pro-hypertensive changes in the kidney involving pre/post-glomerular vessel remodeling as indicated by an apparent reduction in pre-glomerular lumen dimensions, a reduced glomerular filtration capacity and a reduction in the pressure natriuresis relationship.
Angiotensin II↗
Nephron number, renal function, and arterial pressure in aged GDNF heterozygous mice.
The loss of one allele for glial cell line-derived neurotrophic factor (GDNF) results in approximately 30% fewer but normal sized glomeruli in young mice. Low nephron number, inherited or acquired, has been linked to increased risk of development of hypertension and renal failure. This study examines whether GDNF heterozygous mice, with an inherent reduction in nephron number, demonstrate a deterioration in renal structure and function and rise in arterial pressure in later life. Fourteen-month-old male GDNF heterozygous (n=7) and wild-type (n=6) mice were anesthetized and prepared for measurement of mean arterial pressure, glomerular filtration rate (GFR), and renal blood flow. After measurement of renal function, kidneys were fixed for stereological determination of total glomerular number and mean glomerular volume. Mean arterial pressure was, on average, 18 mm Hg higher in GDNF heterozygous (98+/-4 mm Hg) than wild-type mice (80+/-2 mm Hg; P<0.01). However, GFR (0.656+/-0.054 versus 0.688+/-0.076 mL/min per g kidney wt) and renal blood flow (5.29+/-0.42 versus 4.70+/-0.34 mL/min per g kidney wt) were not different between groups. Fourteen-month-old GDNF heterozygous mice had approximately 30% fewer glomeruli than wild-type mice (9206+/-934 versus 13440+/-1275; P<0.01) and significantly larger glomeruli (4.51+/-0.39 versus 3.72+/-0.63x10(-4)mm(3); P<0.01). Thus, aged GDNF heterozygous mice maintained a normal GFR and renal blood flow despite reduced nephron numbers. The elevated arterial pressure, glomerular hypertrophy, and hyperfiltration demonstrated in the GDNF heterozygous mice at this age may indicate a compensatory mechanism whereby GFR is maintained in the presence of a reduced nephron endowment.
Aging↗
Autoregulation of renal medullary blood flow in rabbits.
We examined the extent of renal medullary blood flow (MBF) autoregulation in pentobarbital-anesthetized rabbits. Two methods for altering renal arterial pressure (RAP) were compared: the conventional method of graded suprarenal aortic occlusion and an extracorporeal circuit that allows RAP to be increased above systemic arterial pressure. Changes in MBF were estimated by laser-Doppler flowmetry, which appears to predominantly reflect erythrocyte velocity, rather than flow, in the kidney. We compared responses using a dual-fiber needle probe held in place by a micromanipulator, with responses from a single-fiber probe anchored to the renal capsule, to test whether RAP-induced changes in kidney volume confound medullary laser-Doppler flux (MLDF) measurements. MLDF responses were similar for both probe types and both methods for altering RAP. MLDF changed little as RAP was altered from 50 to >or=170 mmHg (24 +/- 22% change). Within the same RAP range, RBF increased by 296 +/- 48%. Urine flow and sodium excretion also increased with increasing RAP. Thus pressure diuresis/natriuresis proceeds in the absence of measurable increases in medullary erythrocyte velocity estimated by laser-Doppler flowmetry. These data do not, however, exclude the possibility that MBF is increased with increasing RAP in this model, because vasa recta recruitment may occur.
Anesthesia↗
Dominance of pressure natriuresis in acute depressor responses to increased renal artery pressure in rabbits and rats.
Increasing renal artery pressure (RAP) activates pressure diuresis/natriuresis and inhibits renal renin release. There is also evidence that increasing RAP stimulates release of a putative depressor hormone from the renal medulla, although this hypothesis remains controversial. We examined the relative roles of these antihypertensive mechanisms in the acute depressor responses to increased RAP in anaesthetized rabbits and rats. In rabbits, an extracorporeal circuit was established which allows RAP to be set and controlled without direct effects on systemic haemodynamics. When RAP was maintained at approximately 65 mmHg, cardiac output (CO) and mean arterial pressure (MAP) did not change significantly. In contrast, when RAP was increased to approximately 160 mmHg, CO and MAP fell 20 +/- 5 % and 36 +/- 5 %, respectively, over 30 min. Urine flow also increased more than 28-fold when RAP was increased. When compound sodium lactate was infused intravenously at a rate equal to urine flow, neither CO nor MAP fell significantly in response to increased RAP. In 1 kidney-1 clip hypertensive rats, MAP fell by 54 +/- 10 mmHg over a 2 h period after unclipping. In rats in which isotonic NaCl was administered intravenously at a rate equal to urine flow, MAP did not change significantly after unclipping (-14 +/- 9 mmHg). Our results suggest that the depressor responses to increasing RAP in these experimental models are chiefly attributable to hypovolaemia secondary to pressure diuresis/natruresis. These models therefore appear not to be bioassays for release of a putative renal medullary depressor hormone.
Animals↗
Acute intrarenal infusion of ANG II does not stimulate immediate early gene expression in the kidney.
ANG II is capable of stimulating expression of immediate early genes such as egr-1 and c-fos in a variety of cultured cells, including cells of renal origin. To investigate whether ANG II can stimulate early growth response gene expression in vivo, we studied the effects of acute renal artery infusion of low-dose ANG II (2.5 ng small middle dot kg(-1) small middle dot min(-1)) or vehicle on the renal expression of c-fos and egr-1 genes in rats. ANG II infusion for 30 or 240 min decreased renal vascular conductance by approximately 13 and 8%, respectively, compared with the vehicle group. Expression of the early growth response genes c-fos and egr-1 was analyzed using Northern blot hybridization. No significant upregulation of c-fos or egr-1 mRNA levels was detected in rats that received ANG II for either 30 or 240 min, compared with the vehicle groups. We conclude that ANG II, at doses that cause significant physiological effects, does not increase the renal expression of c-fos or egr-1 genes over periods of up to 4 h in vivo.
Angiotensin II↗