Biomedical subjects

C Baylis

Publications and source records attributed to C Baylis.

At least 73 records · Page 4Linked to original sources

PubMed1995

Glomerular hemodynamic effects of late pregnancy in rats with experimental membranous glomerulonephropathy.

In these studies, the Fx1A model of accelerated, passive Heymann nephritis was used to produce membranous glomerulonephropathy. Female rats were studied at 7 wk after the administration of the Fx1A antibody either in the virgin state or in late pregnancy. The goals of these experiments were to determine whether preexisting membranous glomerulonephropathy compromises the pregnancy and whether the pregnancy acutely worsens the renal function. Virgin rats with membranous glomerulonephropathy developed massive proteinuria and exhibited glomerular capillary hypertension but without declines in GFR. In late pregnancy, there was no worsening of the proteinuria and glomerular blood pressure fell to normal values. Both afferent and efferent arteriolar resistances increased in pregnant rats with membranous glomerulonephropathy compared with virgins, leading to falls in glomerular plasma flow and single-nephron GFR. There were no histologic abnormalities in the glomeruli of either virgin or late pregnant rats with membranous glomerulonephropathy, and both groups exhibited similar immunoglobulin G and complement deposits. Up to Day 19 (term is 22 days), the pregnancy in rats with membranous glomerulonephropathy appeared uneventful. Thus, this study indicates that the Fx1A model of membranous glomerulonephropathy does not compromise the course of the pregnancy, at least until close to term. Pregnancy lowers glomerular blood pressure in rats with membranous glomerulonephropathy because of both a fall in systemic blood pressure and the atypical renal vasoconstriction, which leads to declines in single-nephron GFR.

Animals↗

PubMed1995

Endothelin modulates the pressor actions of acute systemic nitric oxide blockade.

Acute nitric oxide blockade not only potentiates the vasoconstrictor actions of endothelin but also enhances the synthesis and release of endothelin. To investigate whether the vasoconstrictor actions of acute nitric oxide blockade are modulated by endothelin, studies were conducted in the conscious, chronically catheterized rat. Renal function was measured before and during acute nitric oxide blockade with nitro-L-arginine methylester (L-NAME), L-NAME + endothelin blockade with the endothelin-converting enzyme inhibitor phosphoramidon, or L-NAME + the nonpeptide ETA and ETB receptor antagonist Bosentan. The increases in blood pressure and RVR seen with acute nitric oxide blockade were attenuated by either method of concomitant endothelin blockade. The falls in RPF and GFR were not blunted because endothelin blockade produced parallel reductions of both pressor and renal vasoconstrictor responses to acute nitric oxide blockade. Endothelin blockade alone with either endothelin-converting enzyme inhibitor or the nonpeptide ETA and ETB receptor antagonist had little effect on blood pressure, RPF, or RVR, but increases in urinary sodium excretion and a small decline in GFR were observed with Bosentan. These observations indicate that endogenous endothelin exerts a tonic antinatriuretic action in the normal conscious rat and partially mediates the pressor actions of acute nitric oxide blockade.

Animals↗

PubMed1995

Blood pressure (BP) and renal vasoconstrictor responses to acute blockade of nitric oxide: persistence of renal vasoconstriction despite normalization of BP with either verapamil or sodium nitroprusside.

We have previously reported that acute systemic nitric oxide (NO) blockade in the conscious rat leads to increases in blood pressure and a profound renal vasoconstriction. In the present studies, we investigated the effect on renal vascular resistance of normalization of blood pressure (BP) during acute, i.v. NO blockade with nitro-L-arginine methyl ester (NAME). We found that two separate pharmacologic maneuvers which normalized BP after a transient period of hypertension, namely the NO donor sodium nitroprusside (SNP) or the calcium entry blocker verapamil (VER), did not reverse the increased renal vascular resistance (RVR) produced by acute NAME. In further studies, we prevented the transient increase in BP with the same combination of NAME and VER but with simultaneous administration of the drugs and in this situation, where the kidney was never exposed to a transient rise in renal perfusion pressure, RVR was unchanged compared to control. When we used angiotensin II (AII) as an alternative method of producing acute increases in BP and RVR, we found that VER reversed both the hypertension and the renal vasoconstriction, despite exposure of the kidney to a transient increase in BP. These data suggest that acute, transient exposure of the kidney to an increased BP during NO inhibition produces a sustained increase in RVR that is not reversible with either SNP or VER. The urinary data suggest that the combination of NAME and VER have a synergistic effection the renal tubule to produce a massive natriuretic and diuretic response.

Angiotensin II↗

PubMed1994

Glomerular filtration and volume regulation in gravid animal models.

The gestational increase in glomerular filtration rate that occurs in the normal rat is exclusively the result of an increase in renal plasma flow and there is no sustained increase in glomerular capillary blood pressure during a normal pregnancy. The factor or factors that initiate the gestational renal vasodilatation (and plasma volume expansion) are maternal, not fetoplacental in origin. The precise nature of the initiating factors has not yet been defined, although it is unlikely that the gestational plasma volume expansion can be the sole cause of the increased glomerular filtration rate seen in pregnancy. A number of vasoactive hormones are activated in pregnancy but as yet no clear candidate has emerged as 'the renal vasodilator'. Preliminary evidence suggests that nitric oxide may play an important role in gestational vasodilatation. The normal kidney in pregnancy exhibits substantial renal reserve to amino acid infusion and unimpaired autoregulatory ability despite being already vasodilated by the gestational stimulus. There are marked and sometimes contradictory changes in the various volume sensing and control systems in pregnancy. In general, the sensors perceiving and controlling intravascular volume are reset during a normal pregnancy to enable to mother to accommodate the increased plasma volume without provoking a natriuretic response. Whether the expanded plasma volume of pregnancy is perceived as normal or underfilled is not clear at this time and may vary according to the volume regulatory system. Repetitive pregnancies do not have any cumulative, long-term deleterious effects on renal function, when the underlying function is normal, when it has been compromised by removal of renal mass or during chronic systemic hypertension in the spontaneously hypertensive rat. In the short term, pregnancy does not worsen kidney function when underlying glomerular damage is due to immune stimuli, ablation of renal mass or gentamicin, or in the spontaneously hypertensive rat. Therefore, the chronic renal vasodilatation of pregnancy does not appear to be a damaging entity, unlike other states of low preglomerular arteriolar resistance, studied in the male rat. When pregnancy is superimposed on Adriamycin nephrosis or chronic blockade of nitric oxide, hypertension occurs and renal function declines. In both situations endothelial damage/dysfunction occurs, as is also seen in pre-eclampsia. Further study of the effects of pregnancy in animal models of endothelial dysfunction will prove rewarding.

Animals↗

PubMed1994

Angiotensin II and alpha 1-adrenergic tone in chronic nitric oxide blockade-induced hypertension.

Nitric oxide (NO) is a tonically produced vasodilator that maintains blood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME), which produced sustained hypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT1) receptor with losartan had little effect on BP and RVR in either chronically NO-blocked or normal conscious rats. Acute blockade of the alpha 1-adrenoceptor with prazosin produced moderate similar falls in BP in both chronically NO-blocked and normal rats. The combination of AT1 and alpha 1-adrenoceptor blockade was profoundly antihypertensive and was particularly effective in lowering BP in chronically NO-blocked rats where the hypertension was obliterated. In contrast, the increased RVR persisted in chronically NO-blocked rats receiving combined acute AT1 and alpha 1-adrenoceptor blockade. These observations indicate that, in the sustained phase of chronic NO blockade, the hypertension is largely due to the combined activities of alpha 1-adrenoceptor and AT1 stimulation.

Administration, Oral↗

PubMed1994

Pregnant rats are refractory to the natriuretic actions of atrial natriuretic peptide.

Normal pregnant women and rats undergo a volume expansion. Atrial natriuretic peptide (ANP) is involved in volume homeostasis and is stimulated in response to volume expansion in nonpregnant animals, resulting in natriuresis and diuresis. The conscious, chronically catheterized rat was used to measure mean arterial blood pressure (MABP) and renal responses to administered ANP (160 ng.kg-1.min-1 i.v.) to determine if the actions of ANP are altered by pregnancy. These experiments examined virgin (n = 7) and pregnant rats, studied on gestational days 7-9 (n = 9) and 15-17 (n = 7). Renal clearance studies (with inulin and p-aminohippurate) were conducted in control conditions and during 60 min of ANP infusion. After the ANP infusion, plasma ANP concentrations were measured in virgin and pregnant rats. MABP fell with ANP infusion to similar absolute values in virgins (112 +/- 2 to 80 +/- 6 mmHg), 7- to 9-day pregnant (114 +/- 2 to 91 +/- 3 mmHg), and 15- to 17-day pregnant (107 +/- 2 to 88 +/- 4 mmHg) rats although the percent decline in MABP in 15- to 17-day pregnant rats was less than in virgins. Plasma ANP concentrations were similar in all groups. ANP had no effect on glomerular filtration rate, renal plasma flow, or renal vascular resistance in virgin or pregnant rats. ANP increased sodium excretion in virgins and in 7- to 9-day pregnant rats (+102 +/- 27 and +135 +/- 47%, respectively) but not in 15- to 17-day pregnant animals (+23 +/- 22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Age-dependent glomerular damage in the rat. Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a primary risk factor.

The glomerulus develops progressive injury with advancing age which is particularly pronounced in males and is not the result of any specific disease process. In the present studies conducted in rats, glomerular function and structure were examined in adult (8 mo), elderly (12 mo), and old (19 mo) Munich Wistar rats. Intact males and females and castrated rats of both sexes were studied to determine the role of the sex hormones in mediating age-dependent glomerular damage. Intact males developed glomerular injury and proteinuria whereas females, both intact and ovariectomized, and castrated males were protected from injury. Glomerular blood pressure did not increase with advancing age in any group and did not correlate with glomerular damage. Glomerular volume did increase with advancing age in all groups but did not correlate with glomerular damage. We found that the presence of the androgens rather than the absence of the estrogens provide the risk factor for development of age-dependent glomerular damage. Neither glomerular hypertension nor glomerular hypertrophy provide the primary mechanism by which age-dependent glomerular injury occurs in the intact male.

Aging↗

PubMed1994

Acute nitric oxide blockade amplifies the renal vasoconstrictor actions of angiotension II.

The tone in the renal vasculature is determined by the balance between vasoconstrictor and vasodilator agents. In this study, the effect on renal function was investigated when the acute blockade of the endogenous nitric oxide system was superimposed on a state of high circulating angiotensin II. Studies were conducted in the conscious, unstressed rat measuring renal function before and during acute systemic nitric oxide blockade with nitro-L-arginine methyl ester and with or without concomitant angiotensin II infusion. Nitric oxide blockade alone, in the presence of normal, unstimulated levels of endogenous angiotensin II, caused a large rise in blood pressure and a doubling of renal vascular resistance. The infusion of angiotensin II alone produced a mild rise in systemic blood pressure and a small (30%) rise in renal vascular resistance. When nitric oxide blockade was combined with angiotensin II infusion, the rise in blood pressure was similar to that produced by nitric oxide blockade alone but the increase in renal vascular resistance was much greater (350%), leading to marked declines in renal function. These studies demonstrate that when angiotensin II levels are acutely elevated and are controlling renal vascular tone, nitric oxide is essential for the maintenance of adequate renal perfusion and function.

Angiotensin II↗

PubMed1993

Renal responses to acute angiotensin II inhibition and administered angiotensin II in the aging, conscious, chronically catheterized rat.

Studies of conscious, chronically catheterized, young (3 to 5 months of age) and old (19 to 22 months of age) male Sprague Dawley rats in the baseline state showed that glomerular filtration rate (factored for body weight) was lower and urine flow higher in old compared with young rats. Acute blockade of endogenous angiotensin II (AII) with either converting enzyme inhibitor (CEI) or Losartan (Dupont Merck, Wilmington, DE) caused small variable decreases in blood pressure in both age groups and produced a significant renal vasodilation with increases in renal plasma flow in the older rats. In separate studies using low-dose AII infusion (5 ng/kg body weight/min), an increase in filtration fraction was the only effect seen in both young and old rats with an intact renin/AII system; no effect was seen with CEI. During high-dose AII (20 ng/kg body weight/min), significant and similar increases were seen in blood pressure and renal vascular resistance in old and young rats, and the patterns of blood pressure and renal hemodynamic responses were similar with and without acute CEI. A natriuretic and diuretic response to high-dose AII was seen in young rats with intact endogenous renin/AII, whereas old rats were completely refractory to this action of AII. Against a background of acute CEI, no natriuretic/diuretic response to high-dose AII was seen in either age group. Thus, in the baseline state, renal hemodynamics in the old kidney are controlled by endogenous AII since CEI and Losartan produce renal vasodilation in old but not young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1993

Renal effects of acute endothelial-derived relaxing factor blockade are not mediated by angiotensin II.

The renal responses to acute blockade of the endothelial-derived relaxing factor (EDRF) resemble the renal actions of angiotensin II (ANG II), and the present studies were conducted to establish what role, if any, the endogenous renin-angiotensin system plays in mediating the renal response to acute EDRF blockade. These studies were conducted in the conscious chronically catheterized rat. In control experiments we observed that acute blockade of ANG II synthesis with converting-enzyme inhibition (CEI) led to a fall in blood pressure (BP) and a slight renal vasodilation but no significant change in glomerular filtration rate (GFR) or renal plasma flow (RPF). Urine flow and sodium excretion were unchanged by CEI. Use of the nonpeptide ANG II receptor antagonist losartan had no effect on BP, renal vascular resistance (RVR), GFR, or RPF; however, urine flow and sodium excretion did rise significantly. Because of the high specificity of losartan, this suggests that, in the normal conscious rat, endogenous ANG II does not control renal vascular tone but does enhance renal sodium reabsorption. ANG II blockade with either CEI or losartan had little effect on BP and no effect on the renal hemodynamic responses to acute EDRF blockade. The marked natriuretic and diuretic response to acute EDRF blockade persists during concomitant losartan but is abolished by CEI. These studies suggest that in the conscious rat the renal hemodynamic response to EDRF blockade is not mediated by endogenous ANG II.

Angiotensin II↗

PubMed1993

Locally produced EDRF controls preglomerular resistance and ultrafiltration coefficient.

During systemic acute blockade of endogenous endothelial-derived relaxing factor (EDRF) with N-monomethyl-L-arginine (NMA), a significant rise in arterial blood pressure (BP) occurred in the anesthetized rat. Renal vasoconstriction was also seen, with complex changes in glomerular hemodynamics; both preglomerular (RA) and efferent arteriolar (RE) resistances increased, producing a fall in glomerular plasma flow (QA) and a rise in glomerular blood pressure (PGC). The glomerular capillary ultrafiltration coefficient (Kf) was reduced. The net effect was a small fall in single-nephron glomerular filtration rate (SNGFR). To determine the effects of local EDRF blockade, two additional groups were studied with intrarenal administration of NMA; in the first series, one-tenth of the systemic dose was given, which produced no change in BP, a small renal vasoconstriction with an increase in RA, but no change in RE; thus PGC was unaffected. Kf fell, and a small reduction in SNGFR was seen. With a larger intrarenal dose of NMA (one-fifth systemic) a moderate rise in BP occurred, but only RA rose; RE and PGC were unaffected, and Kf and SNGFR fell. These observations suggest that locally produced EDRF controls RA and Kf and that a rise in RE and PGC is only seen with systemic EDRF blockade when a large rise in BP occurs.

Animals↗

PubMed1993

Glomerular metalloprotease activity in the aging rat kidney: inverse correlation with injury.

Glomerular metalloprotease activity (phenanthroline inhibitable) was measured in cortical homogenates from rat kidneys by use of the rate of degradation of 3H-denatured type I collagen (gelatin). Glomerular metalloprotease activity was similar in male and female kidneys from kidneys from young (4 months) rats (27 +/- 7 and 34 +/- 6 micrograms of [3H]-gelatin degraded/h per milligram of glomerular protein, respectively). Glomerular metalloprotease activity was unaltered by age (18 to 20 months) in intact males but increased two times in old intact females. castrated males, and ovariectomized females. These aging changes correlated inversely with the level of age-dependent glomerular injury, i.e., old intact males had substantially greater glomerular damage than all other old groups. These observations suggest (1) that the androgens are a risk factor for the development of age-dependent glomerular damage: and (2) that an age-dependent increase in glomerular metalloprotease activity may protect against damage by limiting the build-up of glomerular extracellular matrix.

Aging↗

PubMed1992

Renal autoregulation in midterm and late-pregnant rats.

OBJECTIVES: The normal kidney autoregulates (that is, maintains) renal blood flow over a wide range of arterial blood pressures. During normal pregnancy blood pressure falls and the kidney vasodilates. The purpose of this study was to investigate whether renal autoregulatory ability was influenced during pregnancy in the normal rat. STUDY DESIGN: Experiments were conducted on three groups of anesthetized rats, studied in the virgin state, at midterm, and late in pregnancy (gestation lasts 22 days in the rat). Renal blood flow was measured by electromagnetic flow probe at normal renal perfusion pressures, during elevation in renal perfusion pressure with bilateral carotid occlusion, and at subnormal renal perfusion pressures after application of an aortic snare. RESULTS: Blood pressure was similar in midterm and virgin rats but lower in late pregnancy in the control state. Control renal blood flow was similar between virgin and late-pregnant rats but significantly elevated at midterm. During elevation in blood pressure with bilateral carotid occlusion, autoregulation was maintained in all three groups. During graded aortic occlusion, renal autoregulatory ability was lost. The autoregulatory threshold was between 90 and 100 mm Hg for midterm pregnant and virgin rats and was slightly lower at about 88 mm Hg for late-pregnant rats. CONCLUSIONS: Midterm pregnant rats are able to autoregulate renal blood flow as well as virgins are in spite of underlying gestational renal vasodilation. The slight shift in renal autoregulatory threshold seen in late-pregnant rats may prevent the kidney from hypoperfusion during late-gestation hypotension.

Animals↗

PubMed1992

Proximal tubular metalloprotease activity is decreased in the senescent rat kidney.

Proximal tubule brush border membrane-enriched fractions (BBM) from young (4 months) and old (20-22 months) male Sprague-Dawley rats were prepared by differential centrifugation and metalloprotease activity was measured using radioiodinated insulin B chain as substrate. Proteolytic activity is expressed as Units (U), where 1 U = 1 microgram insulin B chain degraded per min and the specific activity is the U per mg BBM protein used in the assay. Total proteolytic activity (measured at pH 7) was decreased 2-fold in BBM from old rats (2.47 +/- 0.11 vs 4.71 +/- 0.35 U/mg BBM protein, p less than 0.01). The chelator, 1,10-phenanthroline, completely inhibited the proteolytic activity in both groups, suggesting that the BBM insulin B chain-degrading activity in both old and young rats was entirely due to metalloproteases. In the presence of thiorphan, a specific inhibitor of the metalloprotease endopeptidase 24.11, approximately 60% inhibition of proteolytic activity occurred in both groups. Thus, total metalloprotease and endopeptidase 24.11 activities are markedly diminished in the proximal tubule of the senescent rat kidney.

Aging↗

PubMed1992

Basal and stimulated plasma atrial natriuretic peptide (ANP) concentrations and cardiac ANP contents in old and young rats.

To investigate the ability of the ageing heart to release atrial natriuretic peptide (ANP) we compared the response of awake, trained, chronically catheterized old (20-21 months) and young (4 months) rats to an acute, hypertonic saline challenge. There were no differences between young and old rats in basal plasma concentration of sodium (PNa; old: 141 +/- 3 meq/l; young: 143 +/- 3 meq/l) or ANP (old: 61 +/- 5 pg/ml; young: 67 +/- 12 pg/ml). Five minutes after acute saline challenge, PNa rose in both groups (old: 146 +/- 2 meq/l; young 149 +/- 1 meq/l) and approximately 3-fold increases in plasma ANP levels (182 +/- 24 pg/ml; young: 179 +/- 42 pg/ml). Hearts of old and young rats were assayed for atrial and ventricular ANP content. Atrial ANP levels were similar in old and young rats (13.5 +/- 3.6 vs. 24.9 +/- 8.7 micrograms/g atrial tissue), whereas ventricular ANP content was approximately 4-fold higher in old vs. young rats (153.7 +/- 39.3 vs. 47.5 +/- 6.4 ng/g ventricular tissue). Thus, the ageing rat heart responds equally as well as the young rat to an acute NaCl challenge.

Aging↗

PubMed1992

The effect of aging on glomerular hemodynamics in the rat.

Glomerular hemodynamics were measured in male Sprague-Dawley rats, aged 4 to 5 months (young) or 20 to 22 months (old). Body weight (BW) and left kidney weights (KW) were higher in old rats than young (BW: 507 +/- 12 g v 342 +/- 11 g, P less than 0.001; KW: 2.0 +/- 0.1 g v 1.3 +/- 0.1 g, P less than 0.001). Arterial blood pressure (AP) was slightly higher in old rats, but within the normotensive range (106 +/- 4 mm Hg v 94 +/- 4 mm Hg, P less than 0.05). Glomerular filtration rate (GFR; factored for KW) was lower in old versus young rats (0.67 +/- 0.05 mL/min/gKW v 1.00 +/- 0.08 mL/min/gKW, P less than 0.02). The cortical surface of the kidney in old (but not young) rats showed marked heterogeneity and single-nephron (SN)GFR was measured only in filtering nephrons and was higher and more variable in old versus young rats. Glomerular blood pressure (PGC) was unchanged in old compared with young rats (53 +/- 4 mm Hg v 55 +/- 2 mm Hg). There was a significantly greater level of glomerular sclerosis (in outer cortical glomeruli) in old versus young rats, and glomerular volume was substantially greater in old rats. This study suggests that age-related glomerulopathy is not primarily mediated by glomerular capillary hypertension.

Aging↗

PubMed1992

Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage.

Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In these studies we investigated the effects of chronic inhibition of basal NO synthesis in the rat for a 2-mo period. Significant systemic hypertension developed in chronically NO-blocked rats compared to controls. Marked renal vasoconstriction was also observed with elevations in glomerular blood pressure (PGC) and reductions in the glomerular capillary ultrafiltration coefficient (Kf). Chronically NO-blocked rats also develop proteinuria and glomerular sclerotic injury compared to controls. These studies therefore describe a new model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous NO synthesis. These observations highlight the importance of the endogenous NO system in control of normal vascular tone and suggest that hypertensive states may result from relative NO deficiency.

Animals↗

PubMed1991

Renal hemodynamics in normal and hypertensive pregnancy: lessons from micropuncture.

Rats are an excellent animal model in which to study the changes in renal hemodynamics associated with normal pregnancy. Midterm pregnant rats exhibit a maximal renal vasodilation leading to increases in glomerular filtration rate (GFR) and renal plasma flow (RPF). Micropuncture studies in midterm pregnant Munich-Wistar rats have shown that single-nephron GFR (SNGFR) increases, due entirely to increases in plasma flow and, importantly, glomerular capillary blood pressure (PGC) remains unchanged in normotensive pregnancy, due to parallel and proportionally similar reductions in preglomerular (RA) and efferent (RE) arteriolar resistance. Despite the chronic gestational renal vasodilation, pregnancy in normotensive rats with either normal kidneys or a variety of underlying diseases, causes no adverse changes in renal function, perhaps because the glomeruli are protected from damaging high PGC. In the presence of systemic hypertension, the renal vasodilation of pregnancy could put the maternal kidney at risk of injury due to increases in PGC. There are few renal functional studies in preexisting, essential hypertension, but micropuncture studies in spontaneously hypertensive rats (SHRs) have shown that repetitive pregnancies in SHRs cause no functional impairment. Surprisingly, SHRs demonstrated no gestational renal vasodilation, although gestational decreases in peripheral resistance certainly occur in the SHR. This absence of gestational renal vasodilation may be a protective mechanism; it remains to be determined whether hypertensive states in which renal vasodilation does occur are associated with increased risk to the maternal kidney.

Animals↗