Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats.

Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 +/- 2 mmHg vs. 38 +/- 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 +/- 0.03 vs. 0.31 +/- 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 +/- 2 to 44 +/- 2 mmHg, P = 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 +/- 0.02-0.42 +/- 0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post-surgery nephrectomized rats and their respective controls when combined (r = 0.89, P = 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r = 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upregulation of the brain renin-angiotensin system in rats with chronic renal failure

Aim: We investigated how the brain renin–angiotensin system is involved in regulation of the sympathetic activity and arterial pressure in rats with chronic renal failure. Methods: Systolic arterial pressure, heart rate and diurnal urinary noradrenaline excretion were measured for 12 weeks in spontaneously hypertensive rats (SHR) with or without subtotal nephrectomy. Expression of mRNAs related to the brain renin–angiotensin system was measured using polymerase chain reaction. Effects of a 6‐day intracerebroventricular infusion of a type 1 angiotensin II receptor antagonist (candesartan) or bilateral dorsal rhizotomy on these variables were also investigated. Results: Systolic arterial pressure and urinary excretion of noradrenaline were consistently higher in subtotally nephrectomized SHR than in sham‐operated SHR (262 ± 5 vs. 220 ± 3 mmHg, P < 0.001; 2.71 ± 0.22 vs. 1.69 ±0.19 ng g^?1 body weight day^?1, P < 0.001). Expression of renin, angiotensin‐converting enzyme and type 1 angiotensin II receptor mRNAs in the hypothalamus and lower brainstem was greater in subtotally nephrectomized SHR than in sham‐operated SHR. Continuous intracerebroventricular infusion of candesartan attenuated hypertension and the increase in urinary noradrenaline excretion in subtotally nephrectomized SHR. Dorsal rhizotomy decreased arterial pressure, urinary excretion of noradrenaline and expression of renin–angiotensin system‐related mRNAs in brains of subtotally nephrectomized SHR. Conclusion: The brain renin–angiotensin system in subtotally nephrectomized SHR appears to be activated via afferent nerves from the remnant kidney, resulting in sympathetic overactivity and hypertension in this chronic renal failure model.     

Renal response to volume depletion and expansion in Milan hypertensive rats

In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (P_int) and oncotic (II_int) pressures, stop-flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (P_a) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (1.5 μl min^-1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (P_int–±_int t than in MNS (-1.3 ± 0.3 vs. ± 0.0 ± 0.5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop-flow pressure (P_sf) in response to loop of Henle perfusion (7.1 ± 0.7 vs. 4.7 ± 0.2 mmHg, P < 0.05). However, during VD the loop of Henle flow that elicited half maximal response in P_sf, the turning point (TP), was equally low in MHS and MNS (13.5 ± 0.6 and 14.3 ± 0.4, respectively). After VE, however, TP increased significantly more in MNS to (32.6 ± 2.1 nl min^-1) then in MHS (to 21.8 ± 0.9 nl min^-1, P < 0.05). It is concluded that the blunting of the TGF resetting in response to VE in MHS rats may well be of importance in the development of hypertension in the MHS strain.     

Acute renal denervation causes time-dependent resetting of the tubuloglomerular feedback mechanism

Renal effects of acute renal denervation (DNX) were studied in anaesthetized rats. In a first series, whole kidney clearance measurements were made 120 and 240 min after unilateral DNX. At 240 min, urine production was 3.59±0.87 μL min^-1 in control kidneys and 7.74±1.97 μL min^-1 in denervated kidneys. The corresponding values for sodium excretion were 0.56±0.17 and 1.41±0.34 μmol min^-1, potassium excretion 0.48±0.08 and 0.97±0.37 μmol min^-1 and glomerular filtration rate (GFR) 0.83±0.08 and 1.05±0.16 mL min^-1, respectively. In a second series, tubuloglomerular feedback (TGF) characteristics were determined with the stop-flow pressure (P_sf) technique. With increasing time, the sensitivity of the TGF mechanism diminished in denervated rats, as indicated by an increased turning point (TP). TP was significantly increased 2 h after DNX from 19.1±1.13 in control to 25.9±1.10 nL min^-1. TP was further increased 4 h after DNX to 37.3±3.12 nL min^-1. However, the maximal TGF response to increased flow in the late proximal tubule was not altered. But, P_st was significantly higher in DNX rats than in the controls (47.4±1.01 vs. 43.0±1.53 mmHg) in spite of a lower blood pressure (107±2.9 vs. 119±2.2 mmHg). We conclude that intact renal nerves are essential for the setting of the TGF sensitivity and hence the regulation of GFR     

Angiotensin-II stimulates nitric oxide release in isolated perfused renal resistance arteries

 Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM and 1000 nM ANG II increased NO-oxidation current by 85±18 pA (n = 11), 148±22 pA (n = 11), and 193±29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4±0.5 nM, 6.1±1.1 nM, and 8.2±1.3 nM, respectively. Neither LOS (1 μM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers markedly blunted NO release in response to ANG II (10 nM): 77±6% inhibition with LOS (n = 8) and 63±9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries, and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent NO release. Received: 24 September 1997 / Accepted: 20 October 1997     

Decreased renal haemodynamic response to inhibition of nitric oxide synthase in subtotally nephrectomized rats

To assess the renal haemodynamic response to manipulations of the nitric oxide (NO) system, we examined subtotally nephrectomized (SNX) rats and control rats (CON) 28 days after their operation. Bolus infusions of the NO synthase inhibitor N ^G-nitro-l-arginine (l-NA) were given intravenously at doses of 2 mg/kg and 10 mg/kg. Blood pressure was measured intra-arterially, glomerular filtration rate was measured by inulin clearance and fractional changes in renal blood flow (RBF) were determined by a Doppler flow probe. Both doses of l-NA caused a similar and dose dependent increase in mean blood pressure in both SNX and CON rats. In contrast, the decrease in RBF and the increase in the renovascular resistance index (RVRI) was less in SNX rats as compared to CON rats (RBF = –70.1±2.2% of baseline vs –52.7±5.2%, P<0.01; RVRI = +177±9% of baseline vs +243±24%, P<0.05). These changes were not affected by autonomic blockade (hexamethonium), or by blockade of the angiotensin II receptor (Losartan). The exogenous NO donor sodium nitroprusside (0.5 and 1.5 g · kg^–1 · min^–1) lowered mean blood pressure to a similar degree in SNX and CON rats; in contrast, RVRI decreased less in SNX rats (86.9±9.2% of baseline) than in CON rats (68.2±4.6%, P<0.05). We conclude that the reaction of the renal vasculature to manipulations of the NO system is altered in the SNX rats. The data suggest that in the remnant kidney, renovascular resistance is less dependent on endogenous NO and the vascular bed is less sensitive to exogenous NO.     

Intratubular and peritubular capillary hydrostatic and oncotic pressures after chronic renal sympathectomy in the anaesthetized rat

The possible role of peritubular capillary physical forces in the diuretic-natriuretic effects of chronic renal denervation was investigated in Inactin-anaesthetized non-diuretic control (C) and unilaterally denervated (D) rats. Micropuncture techniques were combined with measurement of intratubular and peritubular capillary hydrostatic pressures and afferent and efferent arteriolar plasma oncotic pressures were determined, as well. Compared to data of C rats and of innervated kidneys, marked denervation diuresis and natriuresis were seen without changes in GFR. Both late proximal and early distal (F/P)_In values were significantly lower in D kidneys with similar SNGFR. Afferent (π_a) and efferent (π_e) arteriolar oncotic pressures were unchanged by denervation (C-π_a = 23.3 ± 0.79, π_e = 29.9 ± 0.87 mm Hg; D-π_a = 23.2 ± 0.94, π_e = 29.8 ± 1.04 mm Hg). Proximal intratubular hydrostatic pressure was moderately but significantly higher in D kidneys (C=11.9±0.5, D=13.7±0.3 mm Hg,P<0.01), while peritubular capillary pressures were: efferent arteriole (C=13.9±0.5, D=13.4±0.6 mm Hg, NS). It is concluded that the tubular effects of chronic renal sympathectomy are not dependent on changes in Starling forces of the peritubular environment.     

Acute effects of C-peptide on the microvasculature of isolated perfused skeletal muscles and kidneys in rat

The C-peptide has recently been suggested to have beneficial effects in several organs and improve glycaemic control in human type I diabetes, while there were no such effects in healthy controls. The exact mechanisms behind these effects are, however, not clear. In an attempt to study the actions of C-peptide on the microvasculature in normal rats during more controlled conditions, isolated rat hindquarters and kidneys were perfused with albumin solutions in order to obtain low basal concentrations of C-peptide. In rat hindquarters, infusion of C-peptide significantly increased the capillary filtration coefficients (CFC) from 0.035±0.002 to 0.044±0.002 mL min^-1 100 g^-1 mmHg^-1 (P<0.001, n=9) and the permeability surface area product (PS) for vitamin B₁₂ from 3.48±0.29 to 4.02±0.37 mL min^-1 100 g^-1 (P<0.01, n=6). Addition of C-peptide to the perfusate during infusion of sodium nitroprusside did not induce any additional alteration of CFC or PS. The vascular resistance was slightly decreased from 2.74±0.17 to 2.64±0.17 mmHg min 100 g mL^-1 (P<0.01, n=9). These effects of C-peptide are compatible with increases in capillary surface area without alteration of the permeability per se. In isolated rat kidneys perfused at low temperature (8 °C) prepared to inhibit all metabolic processes, C-peptide induced no changes in glomerular filtration rate, total vascular resistance or fractional albumin clearance. Therefore, C-peptide causes active vasodilation of the normothermic microvasculature and hence recruitment of capillaries. These findings support the previous observations in man that C-peptide indeed has biological effects.     

An isolated perfused rat kidney preparation designed for assessment of glomerular permeability characteristics

The aim of the present investigation was to modify the widely used isolated perfused rat kidney preparation to make it more suitable for studies of glomerular permeability to macromolecules. Both kidneys were perfused in situ using separate pumps in two of each other independent systems with Tyrode-solution containing human serum albumin (18.2 g 1^-1). Sodium nitroprusside was administered to induce dilatation and to maintain constant vascular resistance (PRU₁₀₀) during the experiments. The addition of sodium nitroprusside decreased vascular resistance from 0.17 ± 0.05 to 0.09 ± 0.02 mmHg min^-l 100 g^-1 ml^-1 and increased urine flow and glomerular filtration rate. The temperature of the perfusate was reduced from 37°C to 8°C to inhibit tubular reabsorption of protein and fluid, resulting in a urine to plasma concentration ratio of [⁵¹Cr]EDTA of 1.26 ± 0.07. Furosemide reduced the urine to plasma concentration ratio for [⁵¹Cr]EDTA further to 1.15 ± 0.02 and increased glomerular filtration rate. Moreover, by performing the studies at low temperatures (8°C) in the presence of sodium nitroprusside and furosemide it was possible to achieve low and stable albumin fractional clearance values close to those prevailing in vivo. Thus, the described technique, allowing simultaneous perfusions of both kidneys with different solutions, pressures and flows, seem to be well suited for studies of macromolecular transport across glomerular capillaries.     

Flow resistance of the interlobular artery in the rat kidney

The afferent and efferent arterioles are considered to be the most important resistance vessels within the renal vasculature, but there are indications that a pressure drop occurs along the interlobular artery. This pressure drop was investigated from two aspects: 1) In rat kidneys the “stop-flow pressure” in the efferent arterioles was measured with the micropuncture technique. At arterial pressures between 100 and 130 mmHg the stop-flow pressure did not exceed 85 mmHg, which means that the highest pressure at the end of the interlobular artery was 85 mmHg; 2) A mathematical model was constructed, assuming that the diameter of the interlobular artery decreased stepwise from 60 to 10/μm. The artery was divided into 20 segments, each segment containing one afferent arteriole. The flow in the afferent arterioles increased linearly from 100nl · min^-1 in the first segment to 130nl · min^-1 in the last segment. When the pressure in the first segment was 120 mmHg, it was calculated that the pressure in the last segment was 85 mmHg. These findings strengthen the theory that the interlobular artery may participate in the regulation of the intracortical blood flow in the rat kidney. We conclude that the afferent arteriole of the most superficial nephron is nearly maximally dilated and that the juxtamedullary nephron is able to either dilate or constrict its arteriole in normotensive and normohydrated rats.     

Autoregulation of superficial nephron function in the alloperfused dog kidney

Isolated dog kidneys were each pumpperfused by another dog during 4 experimental periods at perfusion pressures (PP) of 21, 17, 13, and 8 kPa, resp. (i. e. 160, 130, 95, and 60 mm Hg). At the 3 highest PP values, the total kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were perfectly autoregulated while at the lowest value both values were significantly lowered. No significant difference was observed between the single nephron GFR (SNGFR) of periods 1 and 2; in period 3 (PP=13 kPa) a lower value was observed (P<0.05). Free flow pressure in proximal convolution (FFP), stop-flow pressure (SFP), and peritubular capillary pressure (PCP) were not different in period 2 than in period 1, but were significantly lower in period 3 (P=0.02–0.05). Effective filatration pressure (EFP) was the highest in period 1, decreasing significantly with decreasing PP. Filtration pressure equilibrium was observed in period 4 at PP 8 kPa. Total blood flow resistance (R_T) fell with decreasing PP, the drop being due to a steep decline in afferent resistance (R_A). Efferent resistance (R_E) increased as PP decreased. Ultrafiltration coefficient (K_f) rose with declining PP both within and outside the autoregulatory range. The results indicate that the lower limit of autoregulation is higher in superficial nephrons than in the whole kidney.     

Addition of purified orosomucoid preserves the glomerular permeability for albumin in isolated perfused rat kidneys

The serum protein, opsomucoid has been shown to be essential for the maintenance of normal capillary permeability in several different organs, including the kidney. Thus, the clearance of albumin was found to be almost fivefold higher in the absence of orosomucoid in a previous study on isolated rat kidneys, perfused with either of two commercially available human albumin solutions of similar composition, but differing in their content of orosomucoid (0.21 g 1^--¹ vs. < 0.005 g 1^--¹), The following experiments were performed in order to verify the hypothesis that this effect on glomerular permselectivity was due to orosomucoid per se and not to other ingredients in the two solutions. Both kidneys of 12 rats were isolated and perfused with identical albumin solutions without orosomucoid, but with the addition of purified orosomucoid (0.25 g 1^--¹) to one of the kidneys. No significant differences in vascular resistance, urine flow or glomerular filtration rate (GFR), which was found to be 27 ± 2 ml min^-1 100 g^-1, were observed between the two groups of kidneys. The fractional clearance of albumin (θ) was initially similar for both kidneys (0.0022 ± 0.0002). In the absence of orosomucoid, θ gradually increased to 0.0076 ± 0.0013 after 1 h of perfusion compared to 0.0040 ± 0.0006 for the kidneys with orosomucoid added to the perfusate (P < 0.001, n= 12). We conclude that the plasma glycoprotein orosomucoid indeed plays an important role in regulating the dynamic properties of the glomerular capillary wall by reducing the permeability towards macromolecules such as albumin.     

High plasmatic angiotensin-converting enzyme (ACE) activity is not correlated with training-induced left ventricular growth in ACE congenic rats

Aim: The aim of this study was to determine the influence of angiotensin‐converting enzyme (ACE) genotype on left ventricular growth after endurance training, in ACE congenic rats with plasma ACE activity twice as high as the donor strain (LOU), thus mimicking the ACE I/D polymorphism observed in humans. Methods: LOU and congenic rats (n = 12) were submitted to an endurance training on a treadmill for 7 weeks, while similar LOU and congenic rats (n = 10) constituted the control groups. Blood pressure, skeletal muscle citrate synthase activity, plasma and left ventricular ACE activity were assessed, and echocardiography was performed before and after the training. Results: Angiotensin‐converting enzyme plasmatic activity of congenic rats (188.2 ± 26.6 in controls and 187.1 ± 22.6 IU in trained rats respectively) was twofold that of the LOU strain (91.9 ± 23.3 in controls, and 88.3 ± 18.1 IU in trained rats respectively). After training, congenic and LOU rats showed a similar significant increase in citrate synthase activity (P < 0.05), and in the left ventricular mass/body mass ratio × 10³: 3.7 ± 0.3 and 3.6 ± 0.6 in the trained congenic and LOU groups, respectively, vs. 3.0 ± 0.1 and 2.9 ± 0.2 in the control congenic and LOU groups respectively (P < 0.05). There was no significant correlation between ACE plasma activity and left ventricular mass in trained or untrained congenic rats. Conclusion: We conclude that training‐induced left ventricular growth is not associated with plasma ACE activity in congenic rats.     

Influence of varying conduit resistance on native heart function with nonpulsatile left heart bypass

Nonpulsatile left heart bypass (NPLHB) represents a new era in cardiac support. We examined the impact of circuit resistance on ventricular loading with NPLHB. Pressure head-flow (H-Q) curves of NPLHB were measured with four grades of circuit resistance in a mock circulation. Lower resistance result, in a shallower H-Q relationship. Based on this results, NPLHB (ventricular apex to descending aorta) with ratios of 75% and 100% was evaluated for its hemodynamic effect in seven anesthetized sheep. Two grades of circuit resistance were generated with each bypass flow. A shallower H-Q relationship was noted at the lower circuit resistance when increased bypass flow fluctuations occurred during a single cardiac cycle (75%:0.9 ±0.4 to 12.2±2.8,P<0.0001; and 100%: 0.6±0.1 to 2.3 ±1.2l/min,P=0.011, with higher and lower resistance, respectively). Improved left ventricular peak pressure also resulted (75%:112±9 to 104±8,P=0.0002; and 100%: 59±26 to 13±5 mmHg,P=0.0045). In conclusion, NPLHB with lower circuit resistance improves the bypass flow response to change in pressure head during the cardiac cycle. This results in increased systolic bypass flow and improved systolic pressure unloading. Therefore, circuit resistance needs to be taken into account when designing NPLHB systems and when assessing their pump effect.     

Impaired glomerular permselectivity for albumin in chemically medullectomized WKY rats

Chemical renal medullectomy with 2-bromo-ethylamine hydrobromide (BEA) has been used to study the importance of the renal medulla in blood pressure regulation. However, conclusive evidence as to whether BEA treatment affects the glomerular barrier is lacking. In the present study, the effects of BEA upon glomerular permselectivity for albumin were studied using isolated kidneys (IPK) perfused at a low temperature (8 °C) to inhibit tubular reabsorption of proteins. Sixteen WKY rats (W_B) received an i.v. injection of BEA (150 mg kg^-1) while 10 rats served as controls (W_C). Volume balance, urinary osmolality and creatinine clearance (GFR) were measured in metabolic cages. Acute paired experiments (n=9) were performed 5–7 weeks after BEA. The rats were anaesthetized and the total in vivo albumin excretion was recorded. The kidneys were then isolated and perfused for measurements of inulin clearance (GFR) and fractional albumin clearance without tubular reabsorption of protein. The nine BEA treated rats showed polyuria and hypoosmotic urine. In vivo GFR was lower in the BEA treated groups when measured with creatinine clearance (459±22 vs. 213±41 μL min^-1 100 g^-1 body wt, P<0.001), while GFR was not significantly changed in the IPK (W_C=135±27, W_B=92±14 μL min^-1 100 g^-1 body wt, n.s.) when perfused at identical pressures. The fractional albumin clearance was increased three times in the BEA group (W_B=9.6±3.4J, P<0.05). Moreover, albumin excretion in vivo was similar in the two groups despite low GFR in the BEA group. We conclude that BEA treatment affects glomerular permselectivity for albumin.     

低分子量肝素降低肾衰模型大鼠IV型胶原蛋白的表达

探讨在肾小球硬化过程中 ,低分子量肝素治疗对细胞外基质和凝血酶受体表达的影响 ,用 5 6肾切除的方法诱导大鼠局灶节段性肾小球硬化模型并给予低分子量肝素治疗 2 0周 ,通过RT PCR和免疫组化法观察低分子量肝素对 5 6肾切除大鼠残肾组织中IV型胶原、凝血酶受体基因表达的影响。低分子量肝素治疗能显著降低 5 6肾切除大鼠蛋白尿、血肌酐、血脂和减轻肾组织的病理改变程度 ,并且显著下调IV型胶原、凝血酶受体mRNA表达。结果提示低分子量肝素可能通过影响凝血酶受体mRNA表达 ,减轻肾小球重塑过程中细胞外基质的异常代谢、沉积。     

Cardiac autonomic function and baroreflex changes following 4 weeks of resistance versus aerobic training in individuals with pre-hypertension

Aim: Cardiac autonomic modulation and baroreflex sensitivity (BRS) are altered in individuals with hypertension. Aerobic exercise (AE) training has been shown to improve both measures, yet little is known about the effects of resistance exercise (RE). The purpose of this study was to examine the heart rate variability (HRV) and BRS following 4 weeks of resistance or aerobic training in a population with borderline high blood pressure (BP). Methods: Twenty‐nine mild hypertensives were recruited and randomly assigned to 4 weeks of RE or AE training. Before and after training, resting measures of HRV frequencies and BRS were obtained. Results: There was a significant decrease in resting systolic BP for both exercise training modes (RE 136 ± 3.0 pre‐ to 132 ± 3.4 post‐training vs. AE 142 ± 4.0 pre‐ to 137 ± 3.6 mmHg post‐training, P = 0.019). Diastolic BP decreased significantly following both exercise training modes (RE 78 ± 1.31 pre to 74 ± 1.1 post vs. AE 80 ± 1.7 pre to 77 ± 1.6 mmHg post, P = 0.002). A significant time by training mode interaction for low frequency : high frequency (HF) ratio (P = 0.017) with AE decreasing the ratio (275.21 ± 67.28 to 161.26 ± 61.49) and RE increasing this ratio (143.73 ± 65.00 to 227.83 ± 59.41). Natural log‐transformed (ln) HRV values showed a time‐by‐training mode interaction for ln HF (P = 0.05) as ln HF increased (4.7 ± 0.38 to 5.4 ± 0.35 ms²) following AE and decreased (5.98 ± 0.37 to 5.76 ± 0.42 ms²) following RE. BRS increased following aerobic training and decreased after resistance training (6.74 ± 1.2 to 7.94 ± 1.3 and 10.44 ± 1.2 to 9.1 ± 1.2 ms mmHg^?1 respectively, P = 0.021). Conclusions: Aerobic exercise improved the autonomic nervous system (increasing vagal tone, reducing sympathovagal balance while increasing BRS) while RE showed no improvements in cardiac autonomic tone and decreased BRS.     

Heterogeniety in regulation of glomerular function

The aim was to study differences in filtration driving forces and glomerular filtration rates between superficial and deep nephrons when urine flow rate was altered at the macula densa region. In young rats stop-flow pressures and single nephron glomerular filtration rates (SNGFR) were measured in the superficial proximal tubules and in the loops of Henle in the papilla. SNGFR was also measured with a modified Hanssen technique. The stop-flow pressures of superficial nephrons amounted to 30.9±0.8 mmHg (mean ± SE) and those of juxtamedullary nephrons to 52.2±1.6 mmHg. In the stop-flow condition the net driving filtration forces were calculated to be about 19 mmHg and 50 mmHg for the superficial and deep glomeruli, respectively. In free flow conditions both net driving forces were calculated to be 19 mmHg. The micropuncture technique gave a SNGFR value for superficial nephrons of 29.6±2.9 and for deep nephrons of 84.1±8.5 nl±min^-1 g^-1 kidney weight (KW). With a modified Hanssen technique the corresponding values were 25.8±3.3 and 27.7±2.9 nl. min^-1.g^-1KW. The tubuloglomerular feedback mechanism is considered to have a powerful regulatory influence on the glomerular filtration rate of deep nephrons.     

Intrarenal administration of angiotensin II does not moderate afferent renal nerve mediated cardiovascular reflexes in the anaesthetized rabbit

Stimulation of the afferent renal nerves in the anaesthetized rabbit by acute reduction in renal perfusion pressure results in a neurally mediated, reflex increase in hindlimb vascular resistance. To determine whether exogenous angiotensin II moderates the reflex, the kidneys of anaesthetized rabbits were vascularly isolated and renal blood flow was occluded acutely, following intrarenal administration of vehicle (0.9% saline) or angiotensin II (0.5 ng), and the hindlimb vascular response was measured. Occlusion of renal blood flow resulted in similar, significant increases in femoral perfusion pressure of 39.7±7.1 mmHg after vehicle and 21.3±8.9 mmHg (P<0.05, n=6) after angiotensin II. The viability of the preparation following repeated episodes of renal blood flow occlusion was tested by a series of three rapid (2–3 min delay) occlusions and three delayed (30 min delay) occlusions. Femoral perfusion pressure rose by 43.1±10.7 mmHg (rapid, P<0.05, n=11) and 64.4±12.3 mmHg (delayed, P<0.05, n = 5) on the first occasion. On the second occasion, the rapid occlusion did not result in a significant increase in femoral perfusion pressure (29.1±8.1 mmHg), but the delayed group did (54.6±22.4 mmHg, P<0.05). On the third occasion, neither group showed a significant change (20.9±16.3 and 30.8±13.5 mmHg). These data suggest that exogenous angiotensin II does not moderate the afferent renal nerve reflex. The decline in hindlimb response following rapid serial occlusion may be attributed to a diminution of an intermediary substance(s) at the nerve receptor site.     

Reflex changes in post- and preganglionic sympathetic adrenal nerve activity and postganglionic sympathetic renal nerve activity upon arterial baroreceptor activation and during severe haemorrhage in the rat

Carlsson , S., Skarphedinsson , J. O., Delle , M., Hoffman , P. & Thorén , P. 1992. Reflex changes in post- and preganglionic sympathetic nerve activity and postganglionic sympathetic renal nerve activity upon arterial baroreceptor activation and during severe haemorrhage in the rat. Acta Physiol Scand 144 , 317–323. Received 19 August 1 991 , accepted 18 November 1991. ISSN 0001–6772. Department of Physiology, University of Göteborg, Sweden and Department of Physiology, University of Iceland, Reykjavik, Iceland. The aim of the study was to compare pre- (pre-aSNA) and postganglionic adrenal sympathetic nerve activity (post-aSNA) and postganglionic renal sympathetic nerve activity (rSNA) in rats during arterial baroreceptor activation and haemorrhage. Adrenal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar rats. To test for pre-aSNA or post-aSNA in adrenal nerves, a ganglionic blocker, trimethaphan (10 mg kg^-1), was administered i.v. If the nerve activity in the adrenal nerve decreased or increased the nerve was considered to contain predominantly post-or preganglionic fibres, respectively. In contrast, the renal nerves exhibit an almost pure postganglionic activity. Baroreceptor activity was tested by activation of baroreceptors, with an a-receptor agonist, phenylephrine, which was slowly infused (0.5–2 mUg kg^-1 min-^l), and to deactivate the baroreceptors the rats were bled down to 50 mmHg for 8 min. The experiments showed that all tested nerve types were baroreceptor dependent. There were no significant differences between the slopes relating nerve activity inhibition to increase in blood pressure (infusion of phenylephrine). During maximal inhibition there was a difference between the rSNA and pre-aSNA, 87 ± 4%, n= 6 , and 68±6%, n = 10 (P < 0.01) of the control value, respectively. The maximal inhibition of post-aSNA was 80 ± 3%, n= 7 , of the control value. During haemorrhage there was a difference between the nerve populations. Pre-aSNA responded with a marked increase within 1.5 rnin (159 ± 29% of control, n= 7) and was then maintained at that level until retransfusion. Post-aSNA responded with i transient increase, reaching 158 ± 19% of control after 1.5min but then decreased slowly during the next 3 min, reaching a value of 89 8 76 at 7.5 rnin of haemorrhage. Finally, rSNA (n = 7) responded with an initial increase (peak value 1.5 min 138 ± 16%) followed by an inhibition to a minimum of 74±12% of control. Our conclusion is that the postganglionic adrenal nerves respond in a similar way to postganglionic renal nerves during baroreceptor activation and also show the same pattern of response during haemorrhage. This might indicate that postganglionic fibres to the adrenal gland and postganglionic renal fibres to the kidney have the same target structures, i.e. blood vessels. and postganglionic adrenal fibres might therefore be of importance in adrenal blood flow regulation.