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C Baylis

Publications and source records attributed to C Baylis.

At least 55 records · Page 3Linked to original sources
PubMed1997

Plasma renin activity and metabolic clearance rate of angiotensin II in the unstressed aging rat.

We conducted studies in conscious chronically catheterized, trained young (3-5 months) and old (18-20 months) rats to assess the impact of aging on baseline renin activity (PRA) and metabolic clearance rate (MCR) of angiotensin II (ANG II). We observed that under unstressed conditions the baseline values of PRA and plasma ANG II were no different in young versus old rats (1.8 +/- 0.2 versus 1.5 +/- 0.2 ng Al/ml/h and 18 +/- 3 versus 15 +/- 2 fmol/ml, respectively). Values of PRA in the present study were similar to those reported by others for old rats, but our young rat values were lower than usually reported. This probably reflects our use of an unstressed preparation. We also observed a blunted increase in PRA in old rats in response to acute converting enzyme inhibition. Overall, our observations suggest that old rats may lose their ability to increase PRA in response to acute stimuli, including perhaps, the stress of blood drawing in emotionally or surgically stressed preparations. We also observed that the MCR of ANG II increased with age, despite similar baseline plasma ANG II concentrations in young and old. This suggests that with aging, an increase occurs in the rate of synthesis of ANG II. These results emphasize the importance of establishing true baseline values for indices of the renin-ANG II system in aging.

Aging↗
PubMed1997

Sensitivity of the segmental renal arterioles to angiotensin II in the aging rat.

With advancing age the old rat kidney becomes tonically vasoconstricted by endogenous angiotensin II (ANGII) (C. Baylis. Am. J. Kid. Dis., (1993) 842). The present study was designed to investigate the sensitivity of the cortical glomerular microvasculature of the old rat kidney (19-22 months of age) to exogenous ANGII, using the in vivo micropuncture technique. In the baseline state, glomerular blood pressure (P(GC)) in old male rate was higher compared to young rats (4-5 months of age). During exogenous ANGII infusion (40 ng/kg/min), a significant rise in arterial blood pressure and renal vasoconstriction occurred in both young and old rats. In young rats, the ANGII induced fall in renal plasma flow (RPF) and glomerular plasma flow (QA) was accompanied by a rise in PGC and thus the glomerular hydrostatic pressure gradient, with little change in Kf. Therefore, the glomerular filtration rate (GFR) and single nephron GFR (SNGFR) were unchanged by ANGII infusion in young rate. In old rats, RPF and QA fell, a rise occurred in PGC and also a fall was seen in the glomerular capillary ultrafiltration coefficient (Kf), thus GFR and SNGFR fell significantly. The magnitude of the pressor and renal vasoconstriction response to ANGII were not affected by age; of interest, ANGII increased preglomerular and efferent arteriolar resistance (RA, RE) and PGC by similar accounts in young and old rats. SNGFR was reduced in old rats, due to the marked ANGII-induced decline in Kf. Neither absolute nor fractional proximal reabsorbtion were affected by ANGII infusion in either young or old rats. by 19-22 months of age, old rats had much more injured glomeruli than young rats. These data demonstrate that the afferent and efferent arterioles had similar sensitivity to exogenous pressor dose of ANGII in both young and old rats, but Kf was more sensitive to ANGII in old rats leading to a significant fall in SNGFR.

Aging↗
PubMed1997

Impact of surgery on nitric oxide in rats: evidence for activation of inducible nitric oxide synthase.

We investigated the effect of euvolemic surgical preparation, on chemical indices of activity of the nitric oxide (NO) system, in anesthetized, acutely prepared rats. The urinary excretion of NO2+NO3 (UNOXV) and cGMP (UcGMPV) increased progressively during the experiment. Pretreatment with aminoguanidine or dexamethasone, inhibitors of inducible NO synthase (iNOS), prevented the increase in UNOXV and UcGMPV but had no impact on mean arterial pressure (BP), renal vascular resistance (RVR) or GFR. Since these variables did not change in the conscious rat, the increased UNOXV results from some aspect of the acute surgical preparation. When acutely prepared rats received L-NAME, a non-specific NOS inhibitor, BP and RVR increased but paradoxical increases in UNOXV and UcGMPV were also seen. Nonselective NOS inhibition (+L-NAME) was fatal in 50% of acutely prepared rats, causing cardiac contracture. The same dose of L-NAME produced no deaths in either conscious chronically catheterized rats or in acutely prepared rats, previously subjected to sterile surgery and acute L-NAME in the conscious state. These data indicate that acute, nonsterile surgery induces expression of iNOS, but that the additional NO generated has no obvious cardiovascular/renal actions. Acute UNOXV and UcGMPV do not predict total NO production, or "hemodynamically active" NO. Generalized NO inhibition in rats acutely stressed by surgery/anesthesia can be fatal.

Animals↗
PubMed1997

Basal and stimulated nitric oxide in control of kidney function in the aging rat.

To investigate the activity of nitric oxide (NO) in control of renal hemodynamics during aging, studies were conducted on conscious Sprague-Dawley rats aged 3-5 mo (young, Y) and 18-22 mo (old, O). Blood pressure (BP) and renal vascular resistance (RVR) were higher in O vs. Y in control, and acute systemic NO synthesis inhibition (NOSI) increased BP and RVR, with an enhanced renal vasoconstrictor response in O. Infusion of the NO substrate L-arginine produced similar, selective renal vasodilation in both groups. The endothelium-dependent vasodilator acetylcholine caused similar falls in BP and RVR, whereas sodium nitroprusside produced an exaggerated depressor response in O vs. Y without falls in RVR in either age group. Urinary excretion of the stable NO oxidation products (NOx) decreased with age, suggesting a decline in the overall somatic NO production. In conclusion, basal tonically produced NO has a more pronounced role in maintenance of renal perfusion in aging, whereas L-arginine- and agonist-stimulated renal vasodilation is not impaired with age. NO production from some source may be reduced with aging, as indicated by falls in 24-h NOX excretion, although the similarity in pressor response and enhanced renal vasoconstrictor response to NOSI suggests that the role of NO in control of total peripheral and renal vascular resistance is maintained.

Acetylcholine↗
PubMed1997

Biosynthesis and homeostatic roles of nitric oxide in the normal kidney.

Nitric oxide (NO) is an important molecular mediator of numerous physiological processes in virtually every organ. In the kidney, NO plays prominent roles in the homeostatic regulation of glomerular, vascular, and tubular function. Differential expression and regulation of the NO synthase (NOS) gene family contribute to this diversity of action. This review explores recent advances in the molecular and cell biology of the NOS isoforms and relates these findings to functions of NO in the control of normal renal hemodynamics, the glomerular microcirculation, and renal salt excretion. Newly recognized molecular diversity of the NOS gene products, factors governing NOS isozyme gene expression and catalytic activity, and the intrarenal distribution of the NOS isoforms are examined. Physiological data regarding the complex roles of NO in the control of renal hemodynamics and the glomerular microcirculation are analyzed, and the effects of chronic NOS inhibition on glomerular function and structure are presented. The contributions of NO to renal salt excretion as well as functional and molecular biological evidence for adaptive changes in NOS isoform expression during variations in dietary salt balance are discussed. Current investigative challenges and goals for future research of renal NO biology are presented.

Animals↗
PubMed1997

Renal nerves do not mediate vasoconstrictor responses to acute nitric oxide synthesis inhibition in conscious rats.

Nitric oxide is a physiologically important peripheral and renal vasodilator. The studies presented here were conducted in the conscious, chronically catheterized, unstressed rat to investigate whether NO interacts with renal efferent sympathetic nerve activity in control of blood pressure, renal vascular resistance, and sodium excretion. Renal clearance studies were conducted in normal rats with innervated kidneys and in a separate group of rats with chronic, bilateral renal denervation. Acute systemic inhibition of NO synthesis with n-nitro L-arginine methyl ester (L-NAME) leads to hypertension, renal vasoconstriction, and natriuresis in rats with intact renal nerves. Chronic renal denervation does not diminish the pressor and renal vasoconstrictor response to NO synthesis inhibition, although the natriuretic response is prevented. Stimulation of renal NO synthesis with the substrate L-arginine produces selective renal vasodilation and a marked osmotic diuresis in the innervated kidney. Renal denervation has little impact on the responses to L-arginine. These studies suggest that in the normal, conscious, chronically catheterized rat in which the sympathetic nervous system is operating at basal levels, renal nerve activity does not contribute to the pressor or renal vasoconstrictor response to NO inhibition or the renal vasodilator response to NO stimulation. These observations contrast with earlier observations made under conditions of stress-induced activation of renal nerve activity.

Animals↗
PubMed1996

Importance of nitric oxide in the control of renal hemodynamics.

The kidney vasculature is under tonic control by nitric oxide (NO) and in cortex, NO controls RA and Kf. Systemic NO inhibition leads to systemic hypertension, increases in RE, mediated by Ang II and ET, and direct effects on RA and Kf. The relationship between NO and other vasoconstrictor systems is variable. In the conscious relaxed animal, vasoconstrictor activity is low, yet acute NO inhibition leads to pressor and renal vasoconstrictor responses. At physiologic levels, ET unexpectedly is a renal vasodilator, possibly via NO generation at RA. When vasoconstrictor activity is high, NO is very important in maintenance of renal perfusion. Chronic L-NAME produces dose dependent systemic and glomerular capillary hypertension and eventual proteinuria and glomerular damage. NO deficiency is key in this process, although the hypertension becomes refractory to L-arginine administration and dependent on Ang II and the SNS, by mechanisms not yet defined. In contrast, the renal vasculature remains fully responsive to L-arginine, suggesting that pressor and renal vascular responses to chronic NO inhibition are separately regulated. NO generated from iNOS does not normally control BP or renal hemodynamics. The relative contributions of NO from bNOS and eNOS, and importance of NOS in different locations in the kidney, remain to be determined.

Animals↗
PubMed1996

Impact of nitric oxide deficiency on blood pressure and glomerular hemodynamic adaptations to pregnancy in the rat.

Studies were conducted to investigate the impact of nitric oxide synthesis inhibition on blood pressure and glomerular hemodynamic adaptations to pregnancy in the rat. In normal pregnancy, urinary excretion of NO2 + NO3 (NOx), reflecting increased nitric oxide (NO) production, progressively increased. Blockade of NO production in virgin and late pregnant Sprague-Dawley rats caused systemic hypertension, increased renal vascular resistance (RVR), reductions in RPF but GFR remained unchanged. In cortical nephrons, preglomerular and efferent arteriolar resistance (RA and RE) were elevated and glomerular capillary blood pressure (PGC) increased markedly. Glomerular plasma flow (QA) and the glomerular capillary ultrafiltration coefficient, Kf, were reduced without change in single nephron glomerular filtration rate (SNGFR) because of the large elevation in PGC. The pressor and glomerular hemodynamic responses to NO blockade were similar in virgins and pregnancy. Urinary NOx excretion was markedly reduced in all groups with chronic NO blockade. Inhibition was incomplete in pregnancy, however, and a level of NO production that was adequate for normal BP and renal function in virgins, led to severe vasoconstriction in pregnancy. The present studies suggest that chronic NO deficiency leads to derangement of the hemodynamic adaptations of pregnancy.

Animals↗
PubMed1996

Nitric oxide and blood pressure: effects of nitric oxide deficiency.

Nitric oxide plays several crucial roles in control of blood pressure and kidney function and in the dietary response to salt in normal humans and animals. Nitric oxide deficiency leads to hypertension and renal damage in experimental animals and may be related to the development of some hypertensive disorders in people.

Animals↗
PubMed1996

Relationship between basal NO release and cyclooxygenase products in the normal rat kidney.

We investigated the physiological regulation of renal function by nitric oxide (NO) and its interactions with the endothelial cyclooxygenase products in the conscious, chronically catheterized rat. A subpressor dose of NO inhibitor nitro-L-arginine methyl ester (L-NAME) produced renal vasoconstriction that was unaffected by cyclooxygenase inhibition with indomethacin (Indo). Acute, high-dose L-NAME produced a pressor response of approximately 40 mmHg and marked renal vasoconstriction. Indo selectively amplified the renal vasoconstriction, whereas inhibition of the thromboxane-endoperoxide receptor had no effect. Chronic NO inhibition for 5 wk led to sustained hypertension and renal vasoconstriction; the latter was amplified by acute Indo. These data suggest that in the normal, conscious rat the kidney is under important NO-dependent tone. There is no obvious interaction between NO and the cyclooxygenase products in control of basal renal function. When systemic NO inhibition is produced with either acute or chronic high-dose L-NAME, the kidney is severely vasoconstricted. The renal vasoconstriction is not ameliorated by thromboxane-endoperoxide antagonism but is exacerbated by cyclooxygenase blockade, suggesting that vasodilator cyclooxygenase products compensate for the renal hypoperfusion because of severe NO deficiency.

Animals↗
PubMed1996

Hypothalamic lesions induce obesity and sex-dependent glomerular damage and increases in blood pressure in rats.

Placement of two symmetrical lesions in the ventromedial hypothalamus of the rat causes massive overeating and obesity. We have studied male (n=8) and female (n=5) Munich-Wistar rats 7 months after induction of obesity and compared them with age-matched controls. Body weight and kidney weight were greater in control males versus females (396 +/- 7 and 1.5 +/- 0.1 g versus 229 +/- 4 and 1.0 +/- 0.1 g, respectively; both P <.001). Both obese males and females were heavier than lean counterparts (592 +/- 30 and 361 +/- 19 g, both P <.001), whereas kidney weight was similar between obese and control rats of each sex (obese males, 1.5 +/- 0.1 g; obese females, 1.1 +/- 0.1 g). Blood pressure was higher in obese versus control males; there was no differences between other groups. Single-nephron glomerular filtration rate was similar in control females and males and obese females but depressed in obese males. Glomerular blood pressure was normal in all groups. Urinary protein excretion and the percentage of sclerosed glomeruli were similar in control females and males and obese females but elevated in obese males. Plasma triglyceride levels were elevated in obesity, particularly in males. We conclude that hypothalamic lesioning induces overeating and obesity and selectively in the male causes hypertension and glomerular damage as well as declines in renal function. This injury is not hemodynamically mediated (glomerular blood pressure is normal) but may be related to the elevation in plasma triglyceride levels, which has previously been causally linked to glomerular damage in genetically obese rats.

Animals↗
PubMed1996

The aging glomerulus.

Glomerular filtration rate (GFR) decreases with advancing age, particularly in men, although the rate of decrease in GFR is highly variable. Renal vasoconstriction contributes to the decrease in GFR because of increased renal nerve activity, angiotensin II, endothelin, and decreases in vasodilatory prostacyclin levels. Intrarenal nitric oxide activity may be enhanced during aging, perhaps as part of a compensatory response. The atrial natriuretic peptide system is altered during aging, but there is probably no net change in intrarenal hemodynamic actions. Glomerular damage also contributes to age-dependent decreases in GFR. The primary mechanisms are unknown, but they involve a buildup of mesangial extracellular matrix materials. Increases in vasoconstrictor, growth promoting factors, and/or decreases in vasodilator, growth inhibiting factors may contribute. Androgens provide a risk factor. Glomerular hypertension and/or hypertrophy are not primary factors in the development of age-dependent glomerulopathy, but will worsen the process when present.

Aging↗
PubMed1995

Glomerular actions of nitric oxide.

NO, a simple molecule synthesized from L-arginine by NO synthases, has been identified to play an important role in cell communication, cell defense and cell injury. The half life of NO is very short because NO either reacts with superoxide anion (O2-), and/or binds to heme molecules or Fe-S groups present in proteins. The biological effects of NO depend on both the concentration of NO at the site of action as well as upon the specific location where NO is generated. Small quantities of NO are generated by cNOS such as that present in the vascular endothelium, while large quantities of nitric oxide are synthesized by iNOS in response to cytokines or bacterial products. Within the kidney NO generated by endothelial cNOS participates in the regulation of the glomerular microcirculation by modifying the tone of the afferent arteriole and mesangial cells (Fig. 4). In addition, NO generated by macula densa and the afferent arteriole control glomerular hemodynamics via TGF and by modulating renin release. Therefore NO is important in the physiologic regulation of glomerular capillary blood pressure, glomerular plasma flow and the glomerular ultrafiltration coefficient. Through its actions on glomerular pressures and flows, NO may also regulate the macro- and micromolecular traffic through the mesangium. Chronic NO insufficiency causes hypertension and glomerular damage and may be causally involved in the genesis of salt dependent hypertension. Increased NO production may be involved in the early pathogenic hemodynamic changes in diabetes and in the physiologic hemodynamic responses to normal pregnancy. Maintenance of the antithrombogenic properties of the endothelium is another important action of NO which inhibits platelet aggregation and adhesion. Large quantities of NO such as that synthesized by either glomerular cells or macrophages during glomerular inflammation may lead to glomerular injury. A better understanding of the physiology and pathophysiology of NO in the kidney will lead to the development of new therapeutic avenues.

Animals↗
PubMed1995

Glomerular hemodynamic responses to pregnancy in rats with severe reduction of renal mass.

These studies investigate glomerular hemodynamic responses to pregnancy in rats with 5/6th reduction of renal mass of four weeks duration. Both preglomerular and efferent arteriolar resistances (RA and RE) fell significantly at midterm although single nephron glomerular filtration rate (SNGFR) and glomerular plasma flow (QA) were unchanged versus virgins. In late pregnant rats with reduction of renal mass, the gestational fall in RA and RE was maintained and GFR, RPF, SNGFR and QA were higher compared to virgins. The gestational renal vasodilation was prolonged in this model of hypertension versus normals and a peripheral vasodilation is also indicated by the late fall in blood pressure. In virgins with 5/6th reduction of renal mass, PGC is elevated but in pregnant rats PGC fell towards term. The value of Kf was doubled in late pregnancy compared to virgins. All three groups of rats with reduction of renal mass showed similar proteinuria and similar levels of focal glomerular sclerosis, suggesting that pregnancy did not exacerbate the glomerular damage in this model of hypertension and renal disease. A decrease in hematocrit in late pregnancy compared with both virgin and midterm pregnancy indicated a plasma volume expansion. We conclude that when superimposed on hypertension with glomerular damage due to 5/6th reduction of renal mass, pregnancy induced gestational renal and peripheral vasodilation and plasma volume expansion. Since pregnancy was antihypertensive and lowered PGC, there was no hemodynamic basis for pregnancy-associated exacerbation of damage in this model of glomerular injury.

Animals↗
PubMed1995

Acute changes in urinary excretion of nitrite + nitrate do not necessarily predict renal vascular NO production.

NO2 + NO3 (NOx), the stable oxidation products of NO, and cGMP are widely accepted as indices of in vivo NO production. Whether acute changes in urinary excretion of nitrite + nitrate (UNOXV) can be taken to reflect acute changes in renal and/or systemic NO production is not known. The present studies were conducted in the conscious rat to investigate the effect on acute changes in UNOxV, of maneuvers that (a) enhance NO production and (b) act as diuretics. L-arginine (L-arg) and acetylcholine (Ach) produce equivalent NO dependent falls in renal vascular resistance (RVR), but a much greater increase in UNOX V is seen with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in UNOX V, and SNP lowers BP but not RVR and results in a reduced UNOX V. None of the diuretics employed should stimulate the NO system or lower RVR; however, the proximally acting agents, acetazolamide and D-arg increased UNOx V, while the loop diuretic furosemide had little effect. H2O diuresis (a distal event) led to a fall in UNOx V. These data suggest that NOx is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in UNOx V. Also, our results show that the relationship between UNOx V and UcGMP V is unpredictable. Therefore, we conclude that measurements of acute changes in UNOxV and/or UcGMP V should be interpreted cautiously, since they may reflect altered tubular handling of NOx rather than the acute activity of the systemic and/or renal NO systems.

Acetylcholine↗
PubMed1995

Actions of endogenous endothelin on glomerular hemodynamics in the rat.

Both endothelin (ET) ETA/ETB receptors are distributed in the glomerular microcirculation, but their physiological functions, if any, are unknown. We used a nonpeptide mixed ETA/ETB receptor antagonist (Bosentan) and a selective ETA receptor antagonist (BQ-123) to investigate the glomerular hemodynamic actions of endogenous ET in the anesthetized euvolemic rat. Blockade of ETA and ETB receptors with Bosentan produced a small fall in systemic blood pressure and a large fall in glomerular blood pressure due to a significant increase in preglomerular (afferent) arteriolar resistance. Single-nephron glomerular filtration rate was not reduced because of an offsetting rise in the glomerular capillary ultrafiltration coefficient. Blockade of the selective ETA receptor with BQ-123 had no effect on blood pressure or glomerular hemodynamics. These observations indicate that endogenous ET is of physiological importance in control of glomerular hemodynamics. Surprisingly, endogenous ET tonically dilates rather than contracts the preglomerular arteriole, and it also tonically lowers the glomerular capillary ultrafiltration coefficient, probably by contracting the mesangial cell. All physiological glomerular actions of ET are mediated via the ETB receptor.

Animals↗
PubMed1995

Renal effects of acute amino acid infusion in hypertension induced by chronic nitric oxide blockade.

L-Arginine is the physiological substrate of nitric oxide, a vasodilator that controls blood pressure and renal hemodynamics in the basal state. In the present studies, we produced chronic nitric oxide blockade by oral administration of the L-arginine analogue NG-nitro-L-arginine methyl ester, which produced sustained hypertension and increased renal vascular resistance in conscious rats. Acute excess L-arginine had little effect on blood pressure but completely normalized renal vascular resistance and increased renal plasma flow in chronically nitric oxide-blocked hypertensive rats. In contrast to L-arginine, D-arginine had no renal hemodynamic effects in either normal or chronically nitric oxide-blocked rats. Acutely administered glycine was ineffective in vasodilating the chronically nitric oxide-blocked rat kidney, in a dose that produced renal vasodilation in normal rats. These findings indicate the following: (1) Hypertension induced by chronic nitric oxide blockade due to substituted L-arginine analogue cannot be acutely reversed with excess L-arginine, suggesting that the maintenance of the hypertension is not solely caused by competitive inhibition of nitric oxide production; (2) in contrast, the kidney remains responsive to L-arginine whereas the renal vasodilator response to glycine is abolished in this model of hypertension.

Animals↗