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PubMed1983

Comparative renal effects of midazolam and thiopental in humans.

Midazolam is a water-soluble benzodiazepine whose quick onset after intravenous injection, short duration of action, absence of venous irritation, and mild cardiovascular and respiratory effects suggest its use for induction of anesthesia. The renal effects of midazolam-N2O-O2 anesthesia, as determined by renal clearance of injected inulin and para-aminohippuric acid (PAH), in hydrated ASA Class I-II surgical patients (N = 8) were compared in a double-blind fashion with a similar group of patients (N = 9) anesthetized with thiopental-N2O-O2. Except for glomerular filtration rate, there were no significant changes in any of the measured variables (blood pressure, effective renal plasma flow, renal blood flow, and renal vascular resistance). The per cent reduction in glomerular filtration rate in patients given thiopental differed significantly from that in patients given midazolam. This study suggests that midazolam, as opposed to thiopental, offers minimal advantage in maintaining renal performance at least during the period of anesthetic administration.

Anesthesia↗
PubMed1992

Normal renal blood flow measurement using phase-contrast cine magnetic resonance imaging.

RATIONALE AND OBJECTIVES: This study assesses the ability of a cardiac-gated phase-contrast magnetic resonance imaging (MRI) technique to measure renal blood flow (RBF) noninvasively in humans. METHODS: In nine normal volunteers, total RBF in the renal arteries and in the left renal vein was estimated by MRI and correlated with RBF determined by the clearance of para-aminohippuric acid (CPAH) and the hematocrit level. RESULTS: Correlation of RBF estimated from left renal vein flow, with RBF by CPAH-hematocrit, yielded r = .86 (P less than .003). Repeated measurement of RBF by MRI demonstrated a high degree of reproducibility, with coefficients of variation ranging from 4.8% to 8.9%. However, the MRI measurements of arterial flow did not significantly correlate with the standard measurements. CONCLUSIONS: Reproducible noninvasive measurement of normal RBF is possible with the phase-contrast MRI technique used to measure renal venous blood flow.

Adult↗
PubMed1998

Comparative toxic effects of iobitridol and iohexol on the kidney.

RATIONALE AND OBJECTIVES: The authors compare the toxic effects of iobitridol and iohexol, which are nonionic contrast media with equivalent osmolalities and viscosities on the kidney. METHODS: In a rat acute renal failure (ARF) model, iobitridol or iohexol (both at the dose of 2.87 g I/kg) were injected to rats after pretreatment with indomethacin and N omega-nitro-L-arginin methyl ester. The effects on histopathology, creatinine clearance, and urinary N-acethyl-beta-D-glucosaminidase (NAG) activity were assessed. In a rat renal slice system, the slices were exposed to iobitridol or iohexol (both at the concentration range of 17.5-70 mg iodine/mL) for 60 min. The accumulation of para-aminohippuric acid (PAH), an organic anion, and the intracellular potassium content as the indicators of renal tubular injury were measured to assess the direct effects of iobitridol and iohexol on renal tubules. RESULTS: In the ARF model, no significant difference was detected between the effects of iobitridol and those of iohexol on the creatinine clearance and urinary NAG activity 24 hours after the injection. However, iobitridol produced a lower degree and incidence of renal tubular injury of renal proximal tubules (P < 0.001) and distal tubules (P < 0.05) compared with iohexol. In the rat renal slice system, the iobitridol treatment had significantly less effect on the PAH accumulation compared with iohexol (P < 0.001). There were no changes in the intracellular potassium content. CONCLUSIONS: These findings suggest that iobitridol has significantly less toxic effects on the kidney compared with iohexol under the condition of our experiment.

Analysis of Variance↗
PubMedDate not supplied

Systemic and renal hemodynamic effects of single oral doses of felodipine in patients with refractory hypertension receiving chronic therapy with beta-blockers and diuretics.

In 12 patients with primary hypertension (World Health Organization stage 2) inadequately controlled by chronic standard triple therapy, hydralazine was replaced by felodipine, a new vasodilating dihydropyridine derivative, and the acute effects of the drug on central and renal hemodynamics were monitored. Following baseline measurements, an oral solution of felodipine (0.075-0.1 mg/kg) was given. Fifteen minutes after intake of felodipine, a significant hypotensive response was observed, and the maximal response (23% reduction of mean arterial pressure) occurred after 30 min. There was a linear relationship between the changes in mean arterial pressure and log plasma concentration of felodipine. Cardiac output (dye dilution) increased during maximal blood pressure reduction, from 5.3 +/- 1.0 to 6.6 +/- 2.4 L/min (p less than 0.01), partly because of increased heart rate from 57 +/- 4 to 65 +/- 9.1 beats/min (p less than 0.01) and partly because of increased stroke volume from 93 +/- 14 to 104 +/- 33 ml (p less than 0.05). Renal plasma flow (para-aminohippuric acid clearance) increased significantly (p less than 0.05) from 343 +/- 138 to 391 +/- 154 ml/min, while glomerular filtration rate ([51Cr]EDTA clearance) did not change. Arteriovenous noradrenaline difference increased 36% during felodipine therapy, when corrected for blood flow increase. We conclude that felodipine is a calcium inhibitor with potent vasodilating properties.

Administration, Oral↗
PubMed1993

Effects of blocking the angiotensin II receptor, converting enzyme, and renin activity on the renal hemodynamics of normotensive guinea pigs.

The effects of three renin-angiotensin system (RAS) antagonists, DuP 753, a nonpeptide angiotensin II (Ang II) receptor antagonist, MK 521, an inhibitor of converting enzyme, and Ro 42-5892, a human renin inhibitor, on renal function and hemodynamics were investigated in anesthetized, ventilated normotensive guinea pigs. This species was selected because this human renin inhibitor inhibits guinea pig renin. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by [3H]inulinmethoxy and [14C]aminohippuric acid clearances. Animals were perfused with isotonic saline at 0.2 ml/min. After a stabilization period of 1 h, drugs were given as an intravenous (i.v.) bolus (DuP 753, 1; MK 521, 0.1; Ro 42-5892, 1 mg/kg), followed by continuous infusion (DuP 753, 3; MK 521, 0.3; Ro 42-5892, 3 mg/kg/h). These doses have been used to induce slight but significant and similar decreases in mean arterial blood pressure (MABP). The mean changes during 1-h treatment showed similar decreases in MABP: vehicle, -2 +/- 1% (n = 10); DuP 753, -13 +/- 2% (n = 10); MK 521, -15 +/- 2% (n = 10); Ro 42-5892, -13 +/- 3% (n = 10), p < 0.001. Diuresis was unchanged in the four groups. GFR (vehicle, -0.2 +/- 8.4%; DuP 753, +10.7 +/- 6.4%; MK 521, +13.2 +/- 8.6%; Ro 42-5892, +37.2 +/- 7.5%, p < 0.01) and RBF (vehicle, -0.7 +/- 6.6%; DuP 753, +10.5 +/- 6.8%; MK 521, +16.4 +/- 6.8%; Ro 42-5892, +37.9 +/- 7.8%, p < 0.01) increased in parallel with the three drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1998

Effects of ANF infusion on the renal responses to lower-body negative pressure in humans.

To investigate the role of atrial natriuretic factor (ANF) in renal responses to a decrease in central blood volume, we examined the effects of ANF infusion on renal function and hormones during prolonged lower-body negative pressure (LBNP). Ten healthy volunteers participated in two experimental sequences, each comprising a 120-min baseline period followed by the application of -20 mm Hg LBNP for 90 min. During one of the two sequences, ANF was infused throughout LBNP application at the constant rate of 2.5 ng/kg/min. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by using inulin and p-aminohippuric acid clearance techniques. LBNP induced a significant decrease in ERPF (534 +/- 28 to 457 +/- 26 ml/min; p < 0.05), GFR (120 +/- 2.5 to 112 +/- 2.5 ml/min; p < or = 0.01), in urine excretion (12 +/- 0.9 to 5.6 +/- 0.5 ml/min; p < 0.001), in sodium excretion (0.36 +/- 0.03 to 0.30 +/- 0.02 mmol/min; p < 0.05), and in plasma ANF (19 +/- 3 to 11 +/- 2 pg/ml; p = 0.001) concomitant with an increase in plasma renin activity (PRA; 0.48 +/- 0.09 to 0.87 +/- 0.16 ng/ml/h; p = 0.01) and of forearm vascular resistance (FVR; p < 0.05). The combination of ANF infusion with LBNP led to a slight increase in plasma ANF from baseline (from 20 +/- 2 to 28 +/- 3 pg/ml; p < 0.05). Compared with values obtained during LBNP with saline vehicle infusion, values obtained during LBNP with ANF infusion were similar for ERPF (463 +/- 23 vs. 457 +/- 26 ml/min), for GFR (111 +/- 2 vs. 112 +/- 2 ml/min), and for urine excretion (7 +/- 0.6 vs. 5.6 +/- 0.5 ml/min; p = 0.07), but greater for fractional excretion of sodium (2.38 +/- 0.25% vs. 1.91 +/- 0.11%; p < 0.05) and FVR (p < 0.05), and smaller for PRA (0.49 +/- 0.1 vs. 0.87 +/- 0.16 ng/ml/h; p < 0.01). These data show that ANF infusion attenuates the antinatriuretic effect of low-level LBNP and its PRA-increasing effects without altering renal hemodynamic responses to LBNP, although there is a decrease in the LBNP-induced forearm vasoconstriction. These results were obtained with plasma ANF levels slightly higher than those in baseline. They support the hypothesis that a decrease in ANF secretion might contribute to the antinatriuretic effect of LBNP.

Adult↗
PubMed1997

Renal function in cyclosporine-treated pediatric renal transplant recipients in relation to gingival overgrowth.

BACKGROUND: Transplant immunosuppression using cyclosporine (CsA) leads to renal dysfunction as well as gingival overgrowth. The underlying alteration in both these lesions is characterized by an excessive accumulation of extracellular matrix components (fibrosis). To investigate the relationship between CsA-induced nephrotoxicity and gingival overgrowth, the renal function as well as the occurrence of gingival overgrowth was evaluated in pediatric renal transplant recipients: 38 boys and 30 girls, ranging in age from 2 to 20 years, who had been on a CsA-based immunosuppressive regimen for at least 12 months. METHODS: Gingival overgrowth was determined on the basis of measurements of sulcus depth and was diagnosed as positive when the probing depth was > or = 4 mm without exhibiting a loss of periodontal attachment. Renal function tests were performed using inulin and para-aminohippuric acid clearances for evaluating glomerular filtration rate, effective renal plasma flow (ERPF), and filtration fraction (FF). RESULTS: Nineteen percent of the children exhibited gingival overgrowth. The occurrence of gingival overgrowth was positively related (P<0.05) to the mean oral daily dose of CsA, the mean CsA trough blood level, and concomitant administration of nifedipine. The children who were on antihypertensive treatment exhibited lower ERPF and significantly higher FF than the normotensive children. The mean FF value was significantly higher (P<0.05) in the children with gingival overgrowth than in those without gingival overgrowth, whereas glomerular filtration rate and ERPF did not differ between the two groups. CONCLUSIONS: The study suggests that there is a positive correlation between the degree of gingival enlargement and changes in renal function expressed as filtration fraction.

Adolescent↗
PubMed1997

Influence of donor and recipient ages and sex on graft function after pediatric renal transplantation.

BACKGROUND: Adult donor grafts adapt to the smaller size of the child recipient by reducing their absolute glomerular filtration rate (GFR) (ml/min). The question arises whether these grafts can increase the absolute GFR when the child recipient grows or whether a child donor graft can better increase its function. The aim of this study was to evaluate the influence of donor and recipient ages and sex on renal function. METHODS: Eighty-five children and adolescents, aged 0.4-20.5 years at transplantation, were monitored annually, by GFR and effective renal plasma flow (ERPF), determined by clearances of inulin and para-aminohippuric acid. The patients received 90 grafts from donors aged 3-67 years. Follow-up time was around 5 years. RESULTS: Absolute GFR and ERPF (ml/min) of grafts from donors <20 years of age (all cadaveric donor grafts) increased during follow-up, resulting in a constant relative GFR and ERPF (ml/min/1.73 m2), whereas absolute GFR and ERPF of grafts from donors >20 years of age remained constant during follow-up, resulting in a significant decrease in relative values. Relative GFR and ERPF fell during follow-up in young recipients (<12 years of age), but remained constant in older recipients (>12 years). Donor and recipient sex did not influence renal function. CONCLUSIONS: Child donor grafts seem better able to increase their function with the growth of the child recipient than adult grafts. However, the limited access to pediatric grafts and the fact that pediatric cadaveric grafts might involve technical problems in connection with grafting restrict their use.

Adolescent↗
PubMed2000

Renal response to a protein load persists during long-term follow-up of children after renal transplantation.

BACKGROUND: Kidney donors and transplant recipients may be at risk of complications from glomerular hyperfiltration of the single kidney. It has been assumed that tests of the existence of renal functional reserve [delta glomerular filtration rate (deltaGFR), delta effective renal plasma flow (deltaERPF)] can be used to demonstrate hyperfiltration. It would therefore be of interest to evaluate the response of the kidney graft to a protein load. i.e., testing the renal reserve and to find out whether a reduction in baseline GFR is preceded by a loss of deltaGFR. METHODS: We repeatedly studied the change in GFR and renal plasma flow (ERPF) after an oral protein load in 30 children after renal transplantation (Tx). Follow-up time was 1.0-8.0 years. Renal function was evaluated with the clearances of inulin and para-aminohippuric acid (PAH). Seven recipient/donor pairs were examined twice (median 0.3 and 4 years, after Tx). RESULTS: The baseline GFR and ERPF remained stable throughout the follow-up and the increase after stimulation (deltaGFR and deltaERPF) did not change in the whole group of Tx children over the years. However, a reduction in the baseline GFR from the first to the last investigation occurred in 23 of 30 children. In the 23 patients whose baseline GFR decreased, deltaGFR was still preserved. In the recipient/donor pairs, the baseline GFR and ERPF were the same, but on the second investigation, donors showed higher deltaGFR. CONCLUSION: Despite fairly low baseline GFR and ERPF values in the Tx children, no change occurs in the capacity to increase GFR and ERPF after a protein load during follow-up, which suggests that they are not maximally hyperfiltrating.

Child↗
PubMed1988

Effects of ephedrine on renal function in patients after major vascular surgery.

The haemodynamic and renal effects of ephedrine were studied in 11 mechanically ventilated patients on the first day after major vascular surgery. Ephedrine, a sympathomimetic agent with alpha-1, beta-1, and beta-2 agonistic activity, was infused into 11 patients to achieve a 20% rise in systolic blood pressure. The doses used were 2-6 micrograms/kg/min, and in six of these 11 patients the dose was then doubled, 4-12 micrograms/kg/min for another renal function test. Blood pressure, heart rate, and cardiac output increased at both dose-ranges. Systolic pulmonary arterial pressure increased by 10% at the first dose-range. Systemic vascular resistance was unchanged and plasma catecholamine levels were unaltered in the present study. Plasma renin activity diminished by 18% and 6%, respectively. Clearance of para-aminohippuric acid increased by 20% and 6%, at the two dose-ranges, while clearance of inulin and urine flow rate increased by 24% and 29%, respectively, at the first dose-range, without further increase during the second dose-range. Fractional chloride excretion, and fractional osmolar clearance were unaltered. Fractional Na+ clearance rose by 30% and 36%, respectively. Fractional free water clearance diminished by 8% at the second dose-range. When comparing the two dose-ranges, HR, systolic and mean BP rose by 8%, 13% and 11%, respectively. Fractional K+ excretion diminished by 30%. We conclude that ephedrine given as a continuous infusion seems to have beneficial effects on renal function in patients after elective major vascular surgery.

Aged↗
PubMedDate not supplied

Effects of cyclosporin A, gentamicin and furosemide on rat renal function: a lithium clearance study.

1. This study applied clearance methods of inulin, lithium, potassium, sodium and para-aminohippuric acid (PAH) for investigation of the effects of cyclosporin A (CyA), furosemide and gentamicin on rat (n = 92) renal function. The drugs were dosed for 2 weeks; CyA 12.5 mg/kg per day, gentamicin 32 mg/kg per day and furosemide 5 mg/kg per day. 2. The questions asked were: could these methods differentiate the effects of drugs with different sites of action, and would gentamicin or furosemide exaggerate the nephrotoxicity of CyA? 3. Furosemide increased sodium clearance (CNa) 74% and fractional sodium clearance (FENa) 105%, while fractional sodium reabsorption in the distal nephron (FDNR) was reduced, compared with placebo-treated controls. 4. Gentamicin reduced CPAH 29% and Cin 37%, while FENa increased 335%. Proximal fractional reabsorption (PFR) and absolute proximal reabsorption (APR) decreased. 5. CyA depressed CPAH 32% and lithium clearance (CLi) 56%, and increased PFR. 6. The effects of CyA and furosemide in reducing renal function were not additive. 7. CyA plus gentamicin reduced CPAH to 35% of the value in untreated controls, equal to 52% of the CPAH of CyA-treated rats; Cin was reduced to 46% of the Cin of CyA-treated rats. 8. Rats given CyA, furosemide and gentamicin had decreased Cin, CPAH and CLi compared with rats given either CyA plus furosemide or gentamicin plus furosemide. 9. Thus, in this investigation of drugs known to have different sites of actions, the differences in renal and tubular function were discernible with the lithium clearance method. 10. The nephrotoxicities of CyA and of gentamicin were additive, while furosemide did not aggravate CyA nephrotoxicity.

Animals↗
PubMed1992

L-arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans.

1. The vascular endothelium produces endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of L-arginine (L-Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para-aminohippuric acid (PAH) and inulin was studied in five normal subjects. 2. Infusion of L-Arg (30 g) caused a significant fall in MBP (-8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters. 3. Neither L-Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7-fold) and after (1.9-fold) L-Arg infusion, but only slightly (1.3-fold) during saline infusion. 4. Urine flow increased more remarkably following L-Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after L-Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary Nox excretion showed positive correlations with urinary flow (r = 0.69, P less than 0.001) and with urinary cGMP excretion (r = 0.60, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Acute effects of candesartan on rat renal haemodynamics and proximal tubular reabsorption.

1. The effects of the specific angiotensin II receptor type I (AT1) antagonist candesartan on renal proximal tubular sodium transport were studied using lithium clearance. The effects of candesartan on mean arterial blood pressure (MABP), renal plasma flow (RPF), glomerular filtration rate (GFR) and sodium and potassium excretion were also investigated. 2. Male Wistar rats were anaesthetized with Inactin (thiobutabarbital sodium; Sigma, St Louis, MO, USA). Clearance markers (8% polyfructosan, 1% para-aminohippuric acid and 4 mmol/l lithium chloride) were given into a jugular vein at the rate of 1.6 mL/h per 100 g bodyweight. Candesartan was given as bolus injection (0.01, 0.1, 0.2, 0.5 and 1.0 mg/kg) followed by 60 min continuous infusion at a rate of 0.5, 5, 10, 25 and 50 microg/min per kg, respectively. 3. The non-depressor dose of candesartan (0.01 mg/kg) did not alter RPF or GFR, whereas diuresis, natriuresis and kaliuresis were observed. The higher doses of candesartan reduced MABP, RPF and GFR, although diuresis, natriuresis and kaliuresis were still observed. 4. Renal tubular sodium and water reabsorption were inhibited after intravenous administration of candesartan independently of an alteration in arterial pressure. Lithium clearance data indicate that the site of inhibition was in the proximal nephron segment.

Angiotensin II↗
PubMed2004

Effect of acute hyperglycaemia on sodium handling and excretion of nitric oxide metabolites, bradykinin, and cGMP in Type 1 diabetes mellitus.

AIMS: The aim of this study was to evaluate the effect of acutely induced hyperglycaemia on renal sodium handling and to explore the role of the bradykinin-nitric oxide-cGMP signalling pathway. PATIENTS AND METHODS: We compared 20 Type 1 diabetic (DM1) patients without microalbuminuria with 15 weight-, age-, and sex-matched healthy controls (C). Clearances of para-aminohippuric acid (CPAH), inulin (Cin), lithium, sodium, and urinary nitrite/nitrate (NOx), cGMP and bradykinin excretion rates were measured in two 90-min periods: a glycaemic clamp-induced euglycaemia (5 mmol/l-period I) and hyperglycaemia (12 mmol/l-period II) (Study 1) and during time-controlled euglycaemia (5 mmol/l-period I and 5 mmol/l-period II) to avoid the effects of time and volume load (Study 2). RESULTS: Cin and CPAH were not significantly different during euglycaemia (period I of Study 1) in DM1 and controls, whereas fractional excretion of sodium was decreased in DM1 (1.84 +/- 0.75 vs. 2.36 +/- 0.67%; P < 0.05) due to an increase in fractional distal tubular reabsorption of sodium (94.01 +/- 1.94 vs. 92.24 +/- 2.47%; P < 0.05). A comparison of changes during Study 1 and Study 2 revealed acute hyperglycaemia did not change renal haemodynamics significantly, while fractional distal tubular reabsorption of sodium increased (DM1: P < 0.05; C: P < 0.01) and fractional excretion of sodium decreased (P < 0.01) in both groups. The urinary excretion rates of NOx were comparable during euglycaemia in DM1 and C. While in C, they significantly increased during Study 1 (period I: 382 +/- 217 vs. period II: 515 +/- 254 nmol/min; P < 0.01) and Study 2 (period I: 202.9 +/- 176.8 vs. period II: 297.2 +/- 267.5 nmol/min; P < 0.05) as a consequence of the water load, no changes were found in DM1. The urinary excretion of bradykinin was lower in DM1 compared with C (0.84 +/- 0.68 vs. 1.20 +/- 0.85 micro g/min; P < 0.01) during euglycaemia; it was not affected by hyperglycaemia. There were no significant differences between DM1 and C and in cGMP urinary excretion rates following hyperglycaemia. CONCLUSION: This study demonstrates that DM1 without renal haemodynamic alterations is associated with impaired renal sodium handling. Moreover, we did not find a relationship between the renal excretion rates of vasoactive mediators and sodium handling due to hyperglycaemia.

Absorption↗
PubMed1977

Relationship between fetal urine production and amniotic fluid volume in normal pregnancy and pregnancy complicated by diabetes.

The hourly fetal urine production rate (HFUPR) was calculated from ultrasonic measurements of fetal bladder volume. A normal HFUPR reference curve, constructed from measurements in 189 normal pregnancies between 24 and 42 weeks gestation, showed a rapid increase of HFUPR from 3-3 to 24-4 ml up to 40 weeks followed by a slight decline. The amniotic fluid volume was estimated by the p-aminohippuric acid method within 12 hours of HFUPR measurements. In 67 normal pregnancies, there was no relationship between HFUPR and amniotic fluid volume measured between 36 and 41 weeks gestation. In 12 patients with fetal growth retardation, a relationship was found between reduced fetal urinary output and low amniotic fluid volume between 36 and 38 weeks gestation. In the 16 diabetic patients studied between 28 and 40 weeks gestation, there was no relationship between HFUPR (within or below normal range) and the high amniotic fluid volume (above 1500 ml in 13 patients). The implication of these findings are discussed.

Amniotic Fluid↗
PubMed1993

Renal effects of i.v. adenosine infusion in humans.

The effects of systemic intravenous (i.v.) infusion of adenosine on renal blood flow and glomerular filtration in eight healthy, awake females have been examined. Renal blood flow and glomerular filtration rate were measured as the clearance of para-aminohippuric acid (PAH) and inulin, respectively. Following basal sampling adenosine was infused i.v. at successive rates of 60 and 80 micrograms kg-1 min-1 for 30 min at each rate. Plasma clearance of PAH showed a minor, but non-significant, increase from 697 +/- 41 to 775 +/- 97 ml min-1. However, the arterial plasma concentration of PAH decreased by 17 +/- 4% (P < 0.001), indicating that there was a small increase in renal blood flow. Inulin clearance was reduced from 123 +/- 14 to 88 +/- 11 ml min-1 1.73 m-2 (P < 0.01). The resulting filtration fraction was reduced from 18 +/- 1 to 11 +/- 1 (P < 0.001). The K+/Na+ excretion ratio increased from a basal value of 10 +/- 1 to 42 +/- 11 (P < 0.01) at the highest dose of adenosine, and renal oxygen consumption decreased from 17 +/- 2 to 9 +/- 1 ml min-1 (P < 0.001). In conclusion, i.v. infusion of adenosine in healthy, awake subjects causes a minor increase in total renal blood flow and a marked reduction in glomerular filtration. This shows that adenosine also exerts a vasodilatory effect in the renal circulation, primarily on postglomerular arterioles. In addition, adenosine may produce an aldosterone-like effect on salt excretion, and a reduction in renal oxygen consumption.

Adenosine↗
PubMed1988

Cardiovascular effects of the novel arteriovenous dilator agent, flosequinan in conscious dogs and cats.

1. Flosequinan (BTS 49 465, 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) a novel arteriovenous dilator agent was orally effective in conscious renal hypertensive dogs and normotensive cats. The hypotensive potency of flosequinan was approximately ten times less than that of hydralazine in renal hypertensive dogs, 10 mg kg-1 and 20 mg kg-1 flosequinan causing similar falls in mean blood pressure to 1 mg kg-1 and 3 mg kg-1 hydralazine respectively. In normotensive cats, 5 mg kg-1 flosequinan caused similar falls to 0.5 and 1.0 mg kg-1 hydralazine. The onset of hypotensive effect after flosequinan appeared to be slightly slower than after hydralazine in the dog and slightly faster than hydralazine in the cat. 2. The degree of tachycardia and increase in plasma renin activity (PRA) for equivalent falls in mean blood pressure in both species was significantly less for flosequinan than for hydralazine (P less than 0.05). 3. In normotensive dogs, flosequinan, 10 and 20 mg kg-1 orally, caused a small but non-significant increase in sodium and chloride excretion and had little effect on urine volume whereas hydralazine, 1 and 3 mg kg-1 orally, caused a marked retention of sodium and chloride ions and a reduction in urine volume (P less than 0.01). 4. Neither flosequinan, 10 mg kg-1 orally, nor hydralazine 1 mg kg-1 orally, affected either glomerular filtration rate measured as creatinine clearance or effective renal plasma flow measured as p-aminohippuric acid clearance in normotensive dogs. 5. The lesser degree of tachycardia and increase in plasma renin activity together with a lack of sodium retaining activity associated with flosequinan suggest that this agent may have potential advantages over existing therapy as an antihypertensive in man.

Animals↗