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C Baylis

Publications and source records attributed to C Baylis.

At least 19 recordsLinked to original sources
PubMed1999

Animal models of preeclampsia.

Some of the maternal symptoms of preeclampsia can be produced by uterine ischemia, although no quadriped spontaneously exhibits this disease. It may be that the combination of upright posture and uteroplacental ischemia are necessary for manifestation of the full syndrome. Chronic nitric oxide synthase inhibition in rats produces a pattern of change that resembles the symptoms of preeclampsia, and the preeclamptic-like response of rats with adriamycin nephropathy and hyperinsulinemia is associated with endothelial dysfunction. These models are definitely of use in preeclampsia research, but because this disease only occurs spontaneously in primates, the definitive studies on preeclampsia will, of necessity, be clinical.

Animals↗
PubMed1999

Acute interactions between endothelin and nitric oxide in the control of renal haemodynamics.

1. Endogenous endothelin (ET) does contribute to control of renal vascular tone via nitric oxide (NO)-dependent vasodilation in the rat. 2. Endothelin mediates some of the renal vascular responses to acute nitric oxide synthase (NOS) inhibition, being particularly important when a rise in renal perfusion pressure occurs. 3. Tonically produced NO blunts the renal vasoconstrictor responses to acutely administered ET. 4. The similarity between the renal vascular responses to ET administration and NOS inhibition is not fortuitous but, in part, reflects important interactions between these vasoactive agents.

Animals↗
PubMed1999

Hemodynamic and renal effects of U-46619, a TXA2/PGH2 analog, in late-pregnant rats.

The vasoconstrictor effects of pressor agents are attenuated during pregnancy. Thromboxane A2 (TXA2) is produced in great quantities during hypertension in pregnancy, and therefore it is important to know whether pregnancy modifies the pressor effects of TXA2. The TXA2 analog U-46619 was infused in anesthetized, acutely prepared and conscious, chronically prepared late-pregnant and nonpregnant female rats to examine its systemic hemodynamic and renal effects. Mean arterial pressure (MAP) and total peripheral resistance (TPR) were lower in anesthetized pregnant than nonpregnant rats (P < 0.01). The infusion of U-46619 into the aortic arch resulted in elevation of MAP only in pregnant rats, due to a greater elevation of TPR (60 +/- 17%) compared with nonpregnant rats (36 +/- 6%, P < 0.05). The pressor effect of intravenously infused U-46619 was also enhanced in conscious pregnant versus nonpregnant rats, and the increase in renal vascular resistance was undiminished. U-46619 increased hematocrit and plasma protein concentration more during pregnancy, which suggested greater reduction of plasma volume. The urinary excretion of sodium (-1.49 +/- 0.25 vs. -0.54 +/- 0.24 micromol/min) and water was reduced more in pregnant than nonpregnant rats during U-46619 (P < 0.01). Thus the MAP and renal effects of the TXA2 analog are exaggerated during pregnancy in the rat.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Endothelin mediates renal vascular memory of a transient rise in perfusion pressure due to NOS inhibition.

We investigated the renal responses to NO synthase (NOS) inhibition with N-monomethyl-L-arginine (L-NMA; 30 mg/kg) in anesthetized rats in which renal perfusion pressure (RPP) to the left kidney was mechanically adjusted. Acute L-NMA increased blood pressure (BP, approximately 20%) and renal vascular resistance (RVR) rose ( approximately 50%) in the right kidneys that were always exposed to high RPP. In group 1, the left kidney was exposed to a transient increase (5 min) in RPP which was then normalized, and the rise in RVR was similar to the right kidney. In group 2 the left kidney was never exposed to high RPP, and the rise in RVR was attenuated relative to the right kidney. In group 3, rats were pretreated with the endothelin (ET) receptor antagonist Bosentan, immediately before exposure of the left kidney to a transient increase in RPP, and the rise in RVR was also attenuated relative to the right kidney. NOS inhibition resulted in a natriuresis and diuresis in the right kidneys, and approximately 50% of the natriuresis persisted in the left kidney of group 2, in the absence of any rise in RPP. ET antagonism completely prevented the natriuresis and diuresis in response to acute L-NMA in both left and right kidneys. These data suggest that transient exposure to high RPP by NOS inhibition prevents an appropriate vasodilatory response when RPP is lowered, due to the intrarenal action of ET.

Animals↗
PubMed1999

Nitric oxide production is low in end-stage renal disease patients on peritoneal dialysis.

To test the hypothesis that nitric oxide (NO) deficiency occurs in end-stage renal disease (ESRD), NO oxidation products (NO2 + NO3 = NOx) and cGMP were measured in blood, urine, and dialysate effluent of peritoneal dialysis (PD) patients and compared with blood and urine of healthy subjects. All subjects were on a controlled low-nitrate diet (approximately 330 micromol/day). NOx and cGMP outputs were significantly reduced in PD patients (334 +/- 50 micromol/24 h and 55 +/- 13 nmol/24 h, respectively) vs. controls (823 +/- 101 micromol/24 h and 149 +/- 46 nmol/24 h). Plasma arginine was borderline low, plasma citrulline was elevated and plasma levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine were approximately five time higher in PD patients (2.2 +/- 0.3 microM) vs. controls (0.4 +/- 0.1 microM). Although blood pressure (BP) was not different between groups at the time of study, 10 of 11 PD patients were on medication for hypertension. These studies demonstrate that total NO production is low in ESRD, and with appropriate caution, we conclude that this NO deficiency may contribute to the increased BP that occurs in ESRD.

Adult↗
PubMed1999

Glomerular filtration rate in normal and abnormal pregnancies.

During normal pregnancy, an early, marked, and sustained increase occurs in glomerular filtration rate (GFR) secondary to renal vasodilation. An optimal increase in GFR is a good predictor of pregnancy outcome. The pregnant rat provides an excellent model of the gestational renal hemodynamic response, and invasive studies in this species have extended our understanding of the glomerular hemodynamic mechanisms involved. Of note, the chronic renal vasodilation of pregnancy is not associated with glomerular hypertension, and pregnancy has no long-term injurious effects when kidney function is normal. The renal vasodilatory response to pregnancy is robust and persists in a range of mild renal diseases and in renal transplant recipients. When maternal renal function is moderately or severely compromised, however, the renal responses during pregnancy are often attenuated, and pregnancy may also accelerate the course of the renal disease. Studies in the rat have indicated a wide range of possible renal hemodynamic responses to pregnancy in rats with underlying kidney damage, which seem to be disease specific. Irrespective of the renal vascular response to pregnancy, there is no evidence to date suggesting that pregnancy leads to glomerular hypertension.

Animals↗
PubMed1999

Pressor and renal vasoconstrictor responses to acute systemic nitric oxide synthesis inhibition are independent of the sympathetic nervous system and angiotensin II.

Acute systemic, nonselective nitric oxide synthesis inhibition (NOSI) causes a marked pressor and renal vasoconstrictor response in the normal conscious chronically catheterized rat. The present studies directly address the question of how these vasoconstrictor responses are related to the combined vasoconstrictor activities of the sympathetic nervous system and angiotensin II. When the alpha adrenoceptors are blocked (with prazosin) the pressor and renal hemodynamic responses to NOSI are unaffected. Combined alpha adrenoceptor and angiotensin II receptor blockade at the same time as NOSI results in no net change in blood pressure while leaving the renal vasoconstrictor response intact. However, when the NOSI is delayed, a substantial and unblunted pressor response is seen. In contrast to the vasoconstrictor responses, the natriuretic and diuretic responses to acute NOSI are prevented by simultaneous alpha adrenoceptor blockade alone and combined with angiotensin II receptor blockade. These findings suggest that the hemodynamic actions of acute NOSI in the unstressed rat are independent of the sympathetic nervous system and angiotensin II. In contrast, the natriuretic/diuretic response to acute NOSI is apparently partly the result of some interaction with the sympathetic nervous system, not, as we had previously suggested, exclusively the result of a pressure natriuresis.

Adrenergic alpha-Antagonists↗
PubMed1998

The role of endothelin in the age dependent increase in renal vascular resistance in the rat kidney.

Endothelin (ET) is a powerful vasopressor agent that is activated in a number of pathophysiologic states where renal perfusion is reduced. Since renal vasoconstriction occurs as part of renal aging, we investigated the possibility that ET may be activated in the old kidney. These experiments involved acutely blocking endogenous ET with Bosentan (a non-peptide mixed antagonist to both ET receptor types ETA and ETB), in Sprague-Dawley male rats of various ages: young (4 5 months), middle-aged (12-13 months) and old (19-20 months). Experiments were performed in chronically catheterized, conscious rats, studied under unstressed conditions. Renal hemodynamics and sodium excretion were measured before and during acute ET receptor blockade. In all three age groups, Bosentan had no effect on glomerular filtration rate (GFR), renal plasma flow (RPF), renal vascular resistance (RVR), blood pressure (BP) or urine flow. Sodium excretion increased significantly with Bosentan but the natriuresis was similar in rats of all ages. These results suggest that ET does not contribute to the renal vasoconstriction of the old rat kidney.

Aging↗
PubMed1998

The acute pressure natriuresis response blunted and the blood pressure response reset in the normal pregnant rat.

OBJECTIVES: Our purpose was to test the hypothesis that the acute pressure natriuresis curve was reset in pregnancy to facilitate the volume expansion. STUDY DESIGN: Studies were done with 14- to 16-day pregnant (n = 8) and age-matched virgin female (n = 6) Sprague-Dawley rats that were under general anesthesia. The left kidney was denervated, and mechanical clamps were placed on the aorta above and below the renal arteries for manipulation of renal perfusion pressure. Rats received intravenous 0.9% sodium chloride (1.5% body weight/h) and a cocktail of vasoactive factors to suppress variation in endogenous hormones. Renal perfusion pressure was varied acutely from 125 to 95 mm Hg, and glomerular filtration rate, renal plasma flow, sodium excretion, and urine flow were measured in both kidneys at each renal perfusion pressure. Data were analyzed by unpaired t test and by homogeneity by slopes. RESULTS: The acute pressure natriuresis curve was blunted in pregnant rats versus virgins, and the renal nerves were not responsible. The blunted natriuretic response in pregnancy was due to loss of tubular epithelial responsiveness to increased blood pressure. CONCLUSION: The pressure natriuretic response is markedly blunted in pregnancy, permitting the cumulative plasma volume expansion to occur. Contrary to nongravid states, blunting of the acute pressure natriuresis curve in pregnancy is not associated with increased blood pressure because of the profound peripheral vasodilation. This suggests an alteration in the mechanism(s) normally linking blood pressure control to the acute pressure natriuresis relationship.

Animals↗
PubMed1998

Blunted pressure natriuretic response in the old rat: participation of the renal nerves.

With advancing age, there is a generalized reduction in the ability of the kidney to generate a natriuretic response and, in addition, the incidence of salt-sensitive hypertension increases. One event that could link these changes is a defect that develops in the pressure natriuresis response of the old kidney. To test this possibility, we conducted studies on the anesthetized, male Sprague-Dawley rat to determine the effect of abrupt alterations of renal perfusion pressure (RPP) on urinary sodium excretion (U(Na)V). Young (3- to 5-month-old), middle-aged (11- to 13-month-old), and old (18 to 20-month-old) rats were studied, and RPP was varied by clamping the aorta during the infusion of a cocktail of vasoactive hormones that suppressed the activity of endogenous factors. The gain of the pressure natriuresis relationship was severely attenuated in the old rat compared with the young and middle-aged rats. This blunting of the pressure natriuresis relationship in the old rat was partially attenuated by acute renal denervation. This effect was not associated with marked alterations in the filtered load of sodium, implying that aging is associated with a loss of the tubular epithelial response to an acute change in RPP. These observations suggest that the blunted pressure natriuresis may have a role in the increased incidence of salt-sensitive hypertension and that increased renal nerve activity may have a contributory role.

Aging↗
PubMed1998

Renal cortical Na+-K+-ATPase activity and abundance is decreased in normal pregnant rats.

During late pregnancy, the rat undergoes massive plasma volume expansion due to cumulative renal sodium retention. In the present study, conducted in virgin, mid- (days 11-13), and late-pregnant (days 18-20) rats, we measured both Na+-K+-ATPase activity (by coupled enzyme assay) and abundance of the alpha-subunits of the Na+-K+-ATPase (by Western and slot blot analyses) in renal cortex, medulla, and brain stem. Unexpectedly, Na+-K+-ATPase in renal cortex, in both stages of pregnancy, is reduced versus the virgin, consistent with our finding of a reduced quantity of the alpha1-subunit. In renal medulla, there is a small rise in activity at midterm, but there is no difference in either activity or abundance of the alpha1-subunit in late pregnancy, when renal Na retention is maximal. In brain stem, where only alpha2- and alpha3-subunits are evident, pregnancy has no impact on enzyme activity or abundance of either isoform. In conclusion, the outcome of these experiments was unexpected in that we did not observe increased renal Na+-K+-ATPase activity in late pregnancy in the rat. In fact, in renal cortex, Na+-K+-ATPase activity and abundance are reduced. Whatever promotes net sodium retention in pregnancy must be capable of overwhelming this and several other strong natriuretic signals.

Animals↗
PubMed1998

Evolution of chronic nitric oxide inhibition hypertension: relationship to renal function.

We conducted longitudinal measurements of blood pressure and renal function in the conscious, chronically catheterized rat before and during acute nitric oxide synthase inhibition (N-nitro-L-arginine methylester [L-NAME], 37 micromol/kg IV) and then chronic administration of oral L-NAME (approximately 37 micromol/kg per 24 hours). These studies specifically investigate the impact on plasma and renal renin as well as volume status during the evolution of this hypertension in rats not subjected to acute experimental stress. Blood pressure progressively increased with chronic administration of L-NAME and reached values greatly above those seen with acute administration of L-NAME. There were parallel increases in renal vascular resistance and development of proteinuria, and glomerular filtration rate began to decline at day 21, coincident with the appearance of renal damage. Twenty-four-hour urinary nitrite and nitrate excretion remained depressed, reflecting reduced nitric oxide synthesis. The plasma renin activity was variable and only increased transiently at 21 days, thus the angiotensin II dependence of this hypertension is not caused by stimulated plasma renin activity. Despite severe hypertension, sodium intake and excretion were unchanged over the 21 days of L-NAME administration. Plasma volume was significantly reduced at days 2 and 12 of L-NAME administration; thus the prolonged plasma volume contraction must result from the acute natriuretic response to the initial acute L-NAME administration.

Animals↗
PubMed1998

The aging kidney: insights from experimental studies.

The rat provides a useful experimental model to study of the mechanisms of kidney aging. As in man, a wide diversity in the renal response to aging occurs in the rat, and because of this variability it is important to always specify experimental conditions, i.e., strain, gender, diet, and environment. Most aging rats display chronic progressive nephrosis, although the rate at which injury develops is highly variable. There are a number of known risk factors that potentiate injury, including male gender, genetic background, obesity, high protein/high calorie diet, and environmental exposure to pathogens. The causes of age-dependent glomerulopathy are multifactorial and include an imbalance between synthesis and degradation of extracellular matrix products, as well as hemodynamic alterations. Of importance, this damage is not inevitable and can be dissociated from normal kidney aging when optimal conditions for successful aging are provided. There is complex and sometimes contradictory information on vasoactive factors. It is, likely, however, that the activity of intrarenal AngII is somehow upregulated in the aging kidney of some, but not all, strains, and alpha 1-dependent renal nerve activity may also be enhanced. The endothelial vasodialtory prostaglandins and NO exert an increasingly important role in the maintenance of renal perfusion with advancing age, although their production may be diminished. In the future, we anticipate that comparison of rats with different genetic backgrounds will help to dissociate true aging from disease.

Aging↗
PubMed1998

Beta-adrenoceptor-stimulated renin release is blunted in old rats.

Plasma renin activity (PRA) was similar in young versus old male Sprague Dawley rats under unstressed conditions (1.3 +/- 0.2 versus 1.8 +/- 0.3 ng angiotensin I/ml per min). Airjet stress increases PRA in young but not old rats (13.9 +/- 3.8 versus 2.9 +/- 0.8 ng angiotensin I/ml per min), respectively. This response is ablated in young rats by beta-adrenoceptor blockade, suggesting that the increased PRA is mediated by beta-adrenoceptors, and this response was blunted in old rats.

Aging↗
PubMed1998

Recent insights into the roles of nitric oxide and renin-angiotensin in the pathophysiology of preeclamptic pregnancy.

Normal pregnancy involves marked maternal hemodynamic adaptations; these are suppressed in preeclampsia, leading to serious complications for mother and baby. The cause of preeclampsia is unknown, but may involve primary pathology at the maternal/fetal interface. However, the systemic manifestations of the disease are associated with widespread maternal vascular endothelial damage and dysfunction. There has been considerable recent interest in the possible roles for nitric oxide (NO) deficiency and for alterations in the renin angiotensin system (RAS) in the pathophysiology of preeclampsia. The following is an overview of the hemodynamic responses to normal pregnancy, an evaluation of the possible roles of NO and the RAS in these adaptations, and a review of the important aspects of these systems in preeclampsia.

Female↗