The role of left atrial receptors in the regulation of renin release in anesthetized dogs

Experiments were performed on anesthetized dogs to further define the role of left atrial cardiopulmonary receptors in the reflex neural control of renin release. Non-hypotensive arterial hemorrhage produced reversible decreases in left atrial pressure and increases in renin release without significant changes in mean arterial pressure or renal blood flow. When non-hypotensive arterial hemorrhage was performed, while keeping left atrial pressure constant via left atrial balloon inflation, no increase in renin release was observed. These experiments indicate that changes in blood volume unaccompanied by changes in arterial pressure are sensed by left atrial cardiopulmonary receptors, which results in renin release mediated by a neural reflex arc involving in the vagus as the afferent pathway and the renal sympathetic nerves as the efferent pathway.     

Glomerular filtraton rate and PCO2 as determinants of lithium reabsorption

To examine whether lithium reabsorption varies in proportion to the bicarbonate-dependent reabsorption of water and chloride, reabsorption was altered by varying P_CO2 and glomerular filtration rate (GFR) in volume-expanded, anesthetized dogs during ethacrynic acid infusion. At constant GFR and plasma bicarbonate concentration, lithium, bicarbonate, chloride and water reabsorption were inversely related to plasma pH during variations in PCO2. Lithium and bicarbonate reabsorption varied by 9±1% and chloride reabsorption by 7±1% as plasma pH was altered by 0.1 unit from plasma pH 7.5. Calculation of reabsorbate concentrations indicated that lithium was reabsorbed as readily as water (reflection coefficient=0). During mechanical constriction of the suprarenal aorta, GFR was reduced at constant plasma pH. Bicarbonate reabsorption fell more than chloride, water and lithium reabsorption. Lithium reabsorption was not significantly reduced until GFR was reduced by 35%. In stop-flow studies during ouabain infusion, urinary lithium concentrations were reduced below plasma concentrations. This is compatible with passive diffusion of lithium along a lumen-positive potential exceeding 10 mV in the diluting segment. Thus, lithium reabsorption behaved as expected for bicarbonate-dependent paracellular reabsorption during variations in P_CO2; when GFR is reduced, an additional component of lithium reabsorption is disclosed.     

Segmental distribution of vascular resistances during ureteral occlusion: The vasoconstrictive effects of angiotensin and CaCl2 differ from those of catecholamines and renal nerve stimulation

Examinations of renal autoregulation and renin release suggest that α-adrenergic agonists, in contrast to other vasoconstrictors, preferentially constrict the preglomerular arteries. To examine this hypothesis, experiments were performed in anesthetized dogs during ureteral occlusion. At a ureteral pressure (UP) of 100 mmHg the afferent arterioles are dilated and mechanical constriction of the renal artery does not alter intrarenal vascular resistances. Whereas angiotensin and CaCl₂ infused into the renal artery reduced renal blood flow (RBF) by 25–30% without reducing UP, renal nerve stimulation reduced RBF and UP in proportion. During angiotensin and catecholamine infusion, measurements of UP and intrarenal venous pressure permitted calculations of preglomerular, efferent vascular and intrarenal venous resistances. Until RBF was reduced by 25%, angiotensin raised both preglomerular and efferent vascular resistances, whereas norepinephrine and the α-adrenergic agonists, phenylephrine and methoxamine raised preglomerular more than efferent vascular resistance. When RBF was reduced by more than 25%, all vasoconstrictors showed a similar pattern with large increments both in preglomerular and efferent vascular resistances. Conclusions: Humoral and nervous stimulation of α-adrenergic receptors reduce glomerular capillary pressure by preferentially constricting the preglomerular arteries and may affect renal autoregulation and renin release by reducing the transmural pressure of the afferent arterioles.     

Relationship between PGE2 and renin release in dog kidneys Effects of afferent arteriolar dilation and adrenergic stimulation

To study the relationship between PGE₂ and renin release from the kidney, examinations were performed on anesthetized dogs during afferent arteriolar dilation. This condition is known to increase renin release and enhance the stimulatory effects on renin release of β-adrenergic agonists, such as isoproterenol. Afferent arteriolar dilation induced by constricting the renal artery or occluding the ureter increased PGE₂ and renin release before, but not after, indomethacin administration. Isoproterenol infusion during afferent arteriolar dilation increased renin release but not PGE₂ release both before and after indomethacin administration. Phenylephrine, an α-adrenergic agonist, which also induces afferent arteriolar dilation, increased PGE₂ and renin release at control blood pressure but not when the afferent arterioles already were dilated by ureteral occlusion. We conclude that afferent arteriolar dilation caused by renal arterial constriction, ureteral occlusion or infusion of phenylephrine increases prostaglandin synthesis which stimulates renin release. The effect of isoproterenol on renin release is independent of prostaglandin synthesis.     

Contrasting effects of lisinopril and nifedipine on albuminuria and tubular transport functions in insulin dependent diabetics with nephropathy.

An open, randomized, cross-over study was undertaken to assess the effects of lisinopril and nifedipine on albumin excretion, renal haemodynamics and segmental tubular reabsorption in overt diabetic nephropathy. The study consisted of a 4-week run-in period, a 3-week active treatment period, a 4-week wash-out period and a second 3-week active treatment period. Twelve patients with type 1 diabetes with albuminuria, mild to moderate hypertension and a serum creatinine level of less than 200 mumol l-1 were included. Lisinopril reduced albumin excretion from 1343 +/- 337 micrograms min-1 to 879 +/- 299 micrograms min-1 (P less than 0.01), whereas nifedipine was without effect, 1436 +/- 336 micrograms min-1 vs. 1319 +/- 342 micrograms min-1. Glomerular filtration rate (GFR) was unchanged by either drug. Both drugs increased effective renal plasma flow (ERPF) by about 20%. No differences between the drugs were observed with regard to their effect on renal haemodynamic parameters. By contrast, nifedipine exerted an inhibitory effect on several proximal tubular transport markers, whereas lisinopril was without effect. The different actions on tubular transport mechanisms exerted by lisinopril and nifedipine may contribute to the observed effect on albumin excretion.     

Haemodynamic conditions for renal PGE2 and renin release during α- and β-adrenergic stimulation in dogs

Constriction of the renal artery and infusion of an α-adrenergic agonist induce autoregulated vasodilation and increase prostaglandin E₂ (PGE₂) and renin release. The enhancement of renin release during autoregulated vasodilation might be mediated by prostaglandins. To examine this hypothesis, experiments were performed in three groups of anaesthetized dogs. In six dogs constriction of the renal artery to a perfusion pressure below the range of autoregulation raised renin release from 2 ± 1 to 27 ± 6 μg AI.min^-1 and PGE₂ release from 1 ± 1 to 10 ± 2 pmol. min^-1. After administration of indomethacin (10 mg. kg^-1 b. wt), PGE₂ release was effectively blocked and constriction of the renal artery raised renin release only from 0.1 ± 0.1 to 6 ± 1 μg AI.min^-1. During subsequent continuous infusion of a β-adrenergic agonist, isoproterenol (0.2 μg. kg^-1.min^-1), constriction of the renal artery raised renin release from 0.1 ± 0.1 to 52 ± 11 μg AI.min^-1, although there was no rise in PGE₂ release. In six dogs, intrarenal infusion of phenylephrine, an α adrenergic agonist, increased PGE₂ and renin release before, but not after, indomethacin administration. In six other dogs, phenylephrine infused during isoproterenol infusion increased renin release equally before and after indomethacin administration. Thus the enhancing effect of constricting the renal artery or infusing an α-adrenergic agonist is not dependent upon prostaglandins. We propose that autoregulated dilation enhances renin release whether the stimulatory agent is a prostaglandin or a β-adrenergic agonist.     

Evidence for bicarbonate-dependent lithium reabsorption in dog kidneys

To examine whether lithium is reabsorbed along a transcellular or a paracellular route, experiments were performed in anesthetized volume-expanded dogs under conditions of constant glomerular filtration rate (GFR). Ouabain, in doses inhibiting about 80 % of Na,K-ATPase, and ethacrynic acid, another inhibitor of transcellular NaCl reabsorption, did not inhibit lithium or bicarbonate reabsorption. Lithium reabsorption increased in proportion to plasma concentration of lithium (P_Li) up to 12 mM, suggesting a passive transport of lithium. During ouabain administration acetazolamide halved bicarbonate reabsorption, the main driving force for paracellular reabsorption, and halved the reabsorption of lithium. The reabsorbate concentration of lithium, calculated from data obtained before and after acetazolamide infusion, was almost equal to P_Li. Mannitol, which reduces paracellular osmotic transport without affecting bicarbonate reabsorption, reduced lithium and chloride reabsorption in the same proportion as acetazolamide (r=0.87). Combined acetazolamide and mannitol administration reduced fractional lithium reabsorption to 0.09±0.02. These data indicate that lithium is not actively transported but reabsorbed passively along a paracellular route by osmotic forces provided by transcellular NaHCO₃ reabsorption.     

CONCENTRATIONS OF CARBOHYDRATE-DEFICIENT TRANSFERRIN IN DIALYSED PLASMA FROM DRUNKEN DRIVERS

Serum carbohydrate-deficient transferrin (CDT) has previouslybeen found to be a sensitive and specific biological markerof excessive alcohol consumption. In order to study the prevalenceof excessive drinking among arrested drunken drivers, CDT wasmeasured in plasma samples from 50 drunken drivers after dialysisagainst 0.9% NaCl. 60% of the drivers had elevated CDT. Whendata on CDT from other studies were used to interpret our CDTresults, it was estimated that at least 60% of the drunken driverswere consuming at least 50 g pure alcohol per day. Drunken driversinvolved in road traffic accidents tended to have higher CDTvalues than other drunken drivers, indicating a higher alcoholconsumption, while drivers below 30 years of age had lower CDTvalues than older ones.     

Contrasting effects of angiotensin converting inhibitor and alpha-1-antagonist on albuminuria in insulin-dependent diabetes mellitus patients with nephropathy

Abstract. Objective . The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (α-1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin-dependent diabetes mellitus patients with nephropathy. Design . The study consisted of a four-week run-in period, a four-week active treatment period, a four-week wash-out period and a second four-week active treatment period. Setting . The study was performed in the out-patient clinic at a university hospital. Subjects . Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (> 200 μg min^?1), mild to moderate hypertension (diastolic blood pressure 85–115 mmHg) and serum creatinine level below 200 μmol L^?1 were included in the study. Main outcome measures . The effect of the drugs on albumin and total protein excretion, β-2-microglobulin, proximal tubular enzyme markers and renal haemodynamics. Results . Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 ± 281 μg min^?1 to 742 ± 246 μg min^?1 (P < 0.01) and total protein excretion from 2.0 ± 0.4 g per 24 h to 1.3 ± 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fraction from 0.21 ± 0.02 to 0.23 ± 0.01 (P < 0.05). The urinary excretion of the proximal enzyme markers N-acetyl-beta-glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of β-2-microglobulin. However, neither the excretion of β-2-microglobulin nor the enzyme markers were affected by either drug. Conclusions . Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.