Involvement of renal nerves and endothelins in the regulation of renal water excretion in diabetes insipidus rats.

The interaction between renal nerves, endothelins acting via endothelin-A receptors and vasopressin in the regulation of renal excretory function was investigated. In conscious intact and renal denervated diabetes insipidus (DI) Brattleboro rats, as well as their controls, Long-Evans (LE) rats, an infusion of 16.4 nmol/kg/min ET(A) receptor antagonist BQ-123 was performed in the course of 50 min. Femoral artery blood pressure, heart rate, Ccr, V x U(Na), V x U(K) and V x U(Cl) did not alter in any of the groups. Urine flow rate diminished by 38.1% (p < 0.02), while urine osmolality increased by 30.3% (p < 0.05) as a result of BQ-123 infusion in the intact LE rats but neither urine flow rate nor urine osmolality changed in the DI rats. In contrast to intact LE rats, BQ-123 infusion in renal denervated LE rats did not alter urine flow rate or urine osmolality. However, urine flow rate in renal denervated DI rats surprisingly decreased by 71.1% (p < 0.01) while urine osmolality increased by 161% (p < 0.001) as a result of BQ-123 infusion. Endogenous endothelins can regulate renal water excretion through ET(A) receptor activation. Renal sympathetic nerves participate in the modulation of renal water excretion influencing the ET(A) receptor-mediated effects of endothelins in the kidney.

Renal nerves and endothelins interaction in the control of renal excretory function in conscious Long-Evans rats.

The role of renal nerves and endothelins, acting at ET(A) receptors, in the regulation of renal excretory function was investigated in male Long-Evans rats. Catheters were placed in the femoral vein for fluid and drug infusion, in the femoral artery for blood pressure recording as well as in the bladder for urine collection. Infusion of 16.4 nmol/kg/min of the ET(A) receptor antagonist BQ-123 for 50 min was performed in freely moving, intact and renal denervated rats. As a result of BQ- 123 infusion, urine flow rate diminished (P < 0.02) and Uosm increased (P < 0.05) in the intact rats, but not in the renal denervated rats. Bilateral renal denervation itself as well as ET(A) receptor inhibition in both intact and renal denervated rats did not change the mean arterial pressure, heart rate, or the excretion of sodium, potassium and chloride. The data obtained suggest an interrelationship between renal nerves and endothelin-A receptors in the regulation of renal water excretion.

Changes of renal function and blood pressure after nitric oxide synthase inhibition in renal-denervated conscious rats.

Conscious male Wistar rats with implanted catheters in femoral artery for blood pressure registration, femoral vein for drug infusion and bladder for urine collection were used. Nitric oxide synthase inhibition (NOSI) was performed by intravenous administration of 10 mg/kg b.w. N(omega)-nitro-L-arginine methyl ester (L-NAME) before and one week after bilateral renal denervation. Renal denervation led to a decrease of urine osmolality (p<0.05). NOSI decreased heart rate (p<0.001) and increased systolic, mean and diastolic artery pressure both in the intact and the renal-denervated rats (p<0.001). The P(MF)/P(HF) ratio in the heart rate spectrum, considered a criterion for the sympathovagal balance decreased after NOSI in intact and in renal-denervated rats (p<0.001) indicating a reduction in the sympathetic tone. The baroreflex sensitivity after NOSI increased both in conscious rats with intact renal nerves and in rats with bilateral renal denervation. In intact rats NOSI increased urine flow rate by 48.7% (p<0.05), sodium excretion by 339.7% (p<0.01) and chloride excretion by 272.1% (p<0.01). In contrast to the intact rats, NOSI in the renal denervated rats decreased their urine flow rate by 35.5% (p<0.05) and did not alter sodium and chloride excretion. So, chronic renal denervation inversed the diuretic and clearly attenuated the natriuretic and chloruretic response to acute NOSI without inhibiting the rise in blood pressure. Therefore, the increased urine flow as well as the sodium and chloride excretion observed after NOSI are not exclusively the result of a pressure diuresis but are somewhat dependent on the renal sympathetic nerve activity. Renal denervation did not change the pattern of sympathovagal balance and baroreflex sensitivity modified by NO-synthase inhibition.

Spectral coherence between blood pressure and inter-beat intervals in hypertension.

Continuous registration of blood pressure (BP) was obtained in 31 normotensives and 76 hypertensives (divided into 3 stages of hypertension) by a method where the blood pressure in a human finger was measured non-invasively in a beat-by-beat fully calibrated manner. From this signal, the power density spectra of inter-beat intervals (IBI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were derived. Total spectral power (TP) and low/high spectral frequency ratios of all spectra were calculated. Cross-correlation analysis between IBI, SBP and DBP spectra showed that the level of amplitude and phase spectral coherence (SC) was strongly dependent of the stage of hypertension. SC was calculated by means of appropriate mathematical algorithms. Multiple step regression analysis pointed out that the observed phenomenon is highly significant for both--the amplitude and the phase SC (p < 0.01).

Renal excretory function in conscious Long Evans and vasopressin deficient (Brattleboro) rats after endothelin-A receptor inhibition.

All experiments were performed on conscious, freely moving male Long Evans as well as Diabetes incipidus (Brattleboro) rats (300-320 g). The endothelin-A (ETA) receptor antagonist BQ-123 (Neosystem) was administered through femoral vein cannula. Arterial blood pressure was measured trough femoral artery catheter. The bladder was cannulated for urine collection via a small suprapubic incision. After a 40 min control period BQ-123 infusion (16.4 nmol/kg/min, 25 microliters/min) was started and continued for 50 min. The effect of 32.8 nmol/kg/min BQ-123 infused in conscious Brattleboro rats was also investigated. Plasma and urine concentrations of sodium, potassium and chloride as well as osmolality were determined. Glomerular filtration rate (GFR) was estimated using the clearance of endogenous creatinine. Endothelin-A receptor inhibition by 16.4 nmol/kg/min BQ-123 infusion in conscious Long-Evans rats decreased urine flow rate by 38.4% (p < 0.02) and increased urine osmolality by 30.3% (p < 0.05). Sodium, potassium, chloride excretion did not alter. Endothelin-A receptor inhibition by 16.4 nmol/kg/min and by 32.8 nmol/kg/min BQ-123 infusion in conscious Brattleboro rats did not produce any change in urine flow rate, urine osmolality or excretion of the electrolytes studied. Endothelins acting via ETA receptors may function as an inhibitor of water reabsorption in the kidneys of conscious rats.

Spectral analysis of heart rate and arterial pressure variability after nitric oxide synthase inhibition.

The experiments were performed on male, conscious Wistar rats. Femoral arterial pressure was registered by Statham GOULD P23 ID pressure transducer connected to MP 100WS BIOPAC work station after analog to digital conversion during 40 minutes long control period. Nitric oxide synthase inhibition was performed by injection of 100 microliters, 10 mg/kg b.w. N-omega-nitro-L-arginine methyl ester (L-NAME) in saline through femoral vein catheter. Twenty minutes later arterial pressure registration was started and was continued for 40 minutes. The pulse-by-pulse values of systolic, diastolic and mean arterial pressure as well as the pulse intervals were measured by peak and rate detectors of the AcqKnowledge 2.0 software. Row data were processed using a virtual instrument developed in our laboratory in the graphical programming environment Lab VIEW 3.1.1. L-NAME increased systolic, diastolic and mean arterial pressure by 16.6%, 25% and 35%, respectively. The PMF/PHF ratio in heart rate spectrum decreased, indicating an increased vagal effect on the heart. Nitric oxide synthase inhibition increased the low-frequency component of systolic arterial blood pressure variability by 39.5%. Nitric oxide is a physiological regulator of rapid fluctuations of arterial blood pressure.

Attempted suicide by poisoning in the Sofia region.

Data on 9235 persons who had attempted suicide and been admitted to hospital over an eight-year period showed that a female:male ratio of 4:1 in young subjects gradually decreased with age; from the age of 79, the number of men slightly exceeded the number of women. More than half the attempts were made by people aged under 24, and the same proportion was unmarried. Attempts occurred mainly after 2 p.m., with the maximum frequency between 8 p.m. and midnight; over the week, the smallest number was on Saturdays. There was a slight seasonal variation, with the highest number in March and the lowest in August.

Intact kidney function during contralateral renal artery clamping in dogs.

Experiments were carried out on 32 Nembutal anaesthetized mongrel dogs from both sexes. After 45 min control period unilateral renal ischemia was achieved by clamping the left renal artery for 90 min. In part of the experiments (n = 8) after clamp removal 3 consecutive 45 min periods were performed. The function of the intact right kidney was investigated. Mean arterial pressure (MAP), heart rate (HR), glomerular filtration rate (GFR), urine flow rate (V), fractional excretions of sodium (FENa), potassium (FEK) and chloride (FECl) and plasma levels of atrial natriuretic peptide, dopamine and antidiuretic hormone were evaluated. During ischemia MAP was elevated from 122.5 +/- 3.1 to 140.2 +/- 2.7 mmHg (p < 0.001), HR decreased from 119 +/- 4 to 102.5 +/- 3.9 beats/min (p < 0.01) as compared to the control period. GFR did not change significantly, while all excretory parameters increased: V from 8.7 +/- 1.2 to 14.5 +/- 1.7 microliters/min/gr kidney tissue (p < 0.05); FENa from 2.3 +/- 0.2 to 3.6 +/- 0.3% (p < 0.01); FEK from 40.0 < 3.5 to 51.2 < 2.8% (p < 0.05); FECl from 1.8 < 0.3 to 2.6 < 0.3% (p < 0.05). MAP remained elevated in the first and the second postischemic periods and was paralleled by the sustained increase in FENa and FECl, while FEK remained higher to the end of the experiment. ANP was significantly elevated during ischemia: on 75 min--p < 0.01 and on 105 min.--p < 0.05. AVP and dopamine showed no statistically significant changes during the investigated periods.(ABSTRACT TRUNCATED AT 250 WORDS)