Effects of renal denervation on the renal responses of anesthetized rats to cyclohexyladenosine

In the present experiments, we tested the hypothesis that renal denervation would attenuate or abolish some of the renal effects of cyclohexyladenosine, a nonmetabolized adenosine receptor agonist. A paired design (left kidney sham-denervated or denervated versus the innervated right kidney) was used in anesthetized rats. Intravenous cyclohexyladenosine (2.3 nmol/min) reduced para-aminohippurate and inulin clearances in both denervated and sham-denervated kidneys; these effects were increased rather than decreased in denervated kidneys. Similarly, cyclohexyladenosine decreased the excretion of Na+ and K+ more in denervated than in innervated kidneys. Renal plasma flow was decreased by cyclohexyladenosine, without a corresponding increase in the arteriorenal venous difference in plasma renin concentrations, and arterial plasma renin concentration decreased in all rats given cyclohexyladenosine, suggesting inhibition of renin secretion. No differences in the latter variables were noted in denervated versus sham-denervated kidneys. Since cyclohexyladenosine produced effects in denervated kidneys which were equal to or greater than the effects in sham-denervated kidneys, it is concluded that these effects are mediated by direct actions, rather than by inhibition of transmitter release from the renal nerves.     

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. -7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renorenal reflexes: interaction between efferent and afferent renal nerve activity.

In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure results in a contralateral inhibitory renorenal reflex response consisting of increases in ipsilateral afferent renal nerve activity, decreases in contralateral efferent renal nerve activity, and increases in contralateral urine flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To study possible functional central interaction among the afferent renal nerves and the aortic and carotid sinus nerves, the responses to renal mechanoreceptor stimulation were compared in sinoaortic denervated rats and sham-denervated rats before and after vagotomy. In contrast to sham-denervated rats, there was an increase in mean arterial pressure in response to renal mechanoreceptor stimulation in sinoaortic-denervated rats. However, there were no differences in the renorenal reflex responses among the groups. Thus, our data failed to support a functional central interaction among the renal, carotid sinus, and aortic afferent nerves in the renorenal reflex response to renal mechanoreceptor stimulation. Studies to examine peripheral interaction between efferent and afferent renal nerves showed that marked reduction in efferent renal nerve activity produced by spinal cord section at T6, ganglionic blockade, volume expansion, or stretch of the junction of superior vena cava and right atrium abolished the responses in afferent renal nerve activity and contralateral renal function to renal mechanoreceptor stimulation. Conversely, increases in efferent renal nerve activity caused by thermal cutaneous stimulation increased basal afferent renal nerve activity and its responses to renal mechanoreceptor stimulation. These data suggest a facilitatory role of efferent renal nerves on renal sensory receptors.     

Pressor responsiveness in renal prehypertensive rabbits with a denervated kidney

Norepinephrine was infused iv at several doses into four groups of conscious rabbits (six per group), and the pressor responses were recorded. The groups were 3-day sham-operated rabbits; 3-day, two-kidney rabbits with unilateral renal artery stenosis (RAS); 3-day, two-kidney rabbits with unilateral renal denervation; and 3-day, two-kidney rabbits with unilateral renal denervation plus RAS of the denervated kidney. The rabbits with RAS of an innervated kidney and those with RAS of a denervated kidney had the same pressor responses to norepinephrine, which were greater than the pressor responses in the sham-operated rabbits or in the rabbits with a denervated kidney but without RAS. Four additional groups of similarly prepared rabbits were infused with norepinephrine at 800 ng/min/kg body wt, and mean arterial pressure and cardiac output were determined before and during norepinephrine infusion. The rabbits with RAS of an innervated or of a denervated kidney had greater increases in total peripheral resistance as well as in mean arterial pressure during norepinephrine infusion than did the two groups of rabbits without RAS. This indicated that the rabbits with RAS also had increased vascular responses to norepinephrine. The concentration of norepinephrine in six denervated kidneys was extremely low as compared to that of six innervated kidneys. Because renal denervation did not diminish pressor and vascular hyperresponsiveness in 3-day RAS rabbits, the signal that originates in the kidney following RAS and that results ultimately in pressor and vascular hyperresponsiveness is not mediated by renal nerves.     

Role of the renal nerves and angiotensin II in the renal function curve.

The relationship between renal perfusion pressure and urinary sodium is involved in arterial pressure regulation. The aim of this study was to investigate the role of renal nerves and angiotensin II in the pressure-natriuresis relationship. Experiments were performed in anaesthetised cats in which one kidney was surgically denervated. Renal perfusion pressure (RPP), renal blood flow (RBF) glomerular filtration rate (GFR, creatinine clearance), urinary volume (V) and sodium excretion (Una + V) were separately measured from both kidneys. RPP was progressively reduced in two consecutive steps by a suprarenal aortic snare. Two groups of animals were studied: the first without any pharmacological treatment (Untreated), the second during treatment with an angiotensin converting enzyme inhibitor (Captopril, 0.4 mg/Kg intravenously followed by an infusion of 0.4 mg/Kg/h). In the Untreated group RPP was reduced from 152.4 +/- 7.3 to 113.6 +/- 5.8 and 83.0 +/- 4.4 mmHg during the first and second step respectively. RBF and GFR were only slightly reduced during the second step of reduced RPP. In control conditions V and UNa + V were greater in the denervated compared to the innervated kidney. The graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. In the Captopril group V and UNa + V were larger than in the Untreated group in both the innervated and the denervated kidney. A decrease of RPP similar to that observed in the Untreated group, produced similar haemodynamic changes. Also in the Captopril group the graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. Matching UNa + V against RPP values significant correlations were found in the innervated and denervated kidneys of both groups. Both renal denervation and ACE inhibition were accompanied by an increased gain of the pressure-natriuresis curve, but only renal denervation shifted the crossing of the pressure axis to the left. In the ACE inhibited animals renal denervation only shifted the curve to the left. In conclusion our data suggest that i) at each level of RPP renal nerves and angiotensin II decrease renal sodium excretion, ii) renal nerves and angiotensin II increase the slope of the renal function curve, iii) renal nerves shift to the right the renal function curve.     

电刺激肾神经传入纤维对肾水钠钾排出的影响

本文探讨肾神经传入纤维对肾排泄功能的影响及其机制。在戊巴比妥钠麻醉猫中,切除双侧颈动脉窦神经、主动脉神经和迷走神经(SAD+VD),电刺激肾神经传入纤维使动脉血压明显升高,去神经肾的尿量,排钠量显著增多,排钾量和肾小球滤过率不变。神经完好肾的排钠量显著增加,尿量、排钾量和肾小球滤过率均无显著变化。在刺激肾神经传入纤维时,将动脉血压控制在对照期血压水平,两侧肾的尿量、排钠量、排钾量显著减少;神经完好肾的肾小球滤过率减少,而去神经肾的肾小球滤过率无显著改变。脊髓横断不能消除神经完好肾上述肾排泄功能的改变,但可消除去神经肾排泄功能的改变。这些结果表明,在SAD+VD猫中,控制动脉血压不变时,刺激肾神经传入纤维可使有神经肾和去神经肾排尿、排钠和排钾减少。在神经完好肾中这些反应可在脊髓水平完成。     

Reflex mechanisms for changes in renal nerve activity during positive end-expiratory pressure

This study was designed to investigate the interaction between carotid sinus baroreceptors and cardiopulmonary receptors in the reflex control of renal nerve activity (RNA) during positive end-expiratory pressure (PEEP) in anesthetized dogs. PEEP at two different levels (10 and 20 cmH2O) was applied to the following groups: animals with neuraxis intact (I group, n = 12); vagal and aortic nerve denervated animals with carotid sinus nerves intact (V group, n = 6); carotid sinus denervated animals with vagal and aortic nerves intact (SD group, n = 6); and carotid sinus denervated animals also having severed vagal and aortic nerves (SAV group, n = 12). Mean blood pressure (MBP), central venous pressure, and mean airway pressure were also simultaneously measured. In the I group, no significant alterations in RNA occurred during PEEP at both levels, even when MBP fell significantly. Although the drop in MBP in the SD group was similar to that in the I group, RNA decreased significantly 10 s after intervention at both PEEP levels, followed by a recovery of RNA toward the control level. In contrast, a significant increase in RNA, which continued until the end of PEEP, appeared in the V group immediately after each intervention. In the SAV group, RNA responses to PEEP, which were observed in the other groups, were abolished. These results provide evidence that during PEEP, renal nerve activity is modified by an interaction between carotid sinus baroreceptors and cardiopulmonary receptors; excitatory effects occur via carotid sinus nerves and inhibitory effects occur via vagal afferents.     

脑室内注射高张盐水抑制近曲小管对水和钠的重吸收

实验在麻醉大鼠上进行。用锂清除率为指标观察脑室内注射高张盐水对近曲小管重吸收水和钠的影响。在切断单侧肾神经的动物中,脑室内注射高张盐水后的锂清除率与肾小球滤过率比值在去神经侧肾脏从0.37±0.04增加至0.51±0.05(P<0.01);神经完好侧肾脏则从0.26±0.03增加至0.31±0.04(P<0.05);双侧肾脏的肾小球滤过率、尿量、尿钠和尿钾量均增加,且去肾神经肾脏的增加幅度高于肾神经完好肾脏。在肾小管微穿刺实验中,脑室内注射高张盐水后,近曲小管末段小管液流量从24.42±1.84nl/min增加至31.86±3.09nl/min(P<0.01),小管液的渗透压无显著变化。以上实验结果表明,脑室内注射高张盐水引起的利尿、尿钠增多反应与肾小球滤过率增加和近曲小管对水、钠重吸收减少有关,体液因素在该反应中可能起主要作用。     

Excretory function of denervated kidney after inhibition of prostaglandin synthesis and furosemide administration in conscious dogs

The experiments were carried out on unanaesthetized dogs with exteriorized ureters for separate urine collection from the left (denervated) and the right (intact) kidney. The osmolality and concentrations of sodium, potassium, calcium, magnesium, zinc, copper, chloride and creatinine were determined in the plasma as well as in the urine of the two kidneys. The function of the denervated and the innervated kidney was compared prior to and after indomethacin administration (5.0 mg/kg b.w.). The excretory function of both kidneys was also compared after furosemide treatment alone (0.5 mg/kg b.w.) as well as indomethacin pretreatment. Renal denervation increased urine flow rate, calcium and copper excretion. After administration, sodium excretion from the denervated kidney was higher than that from the intact one. Calcium excretion of the two kidneys did not differ significantly, while copper excretion from the denervated kidney was diminished, Furosemide administration after pretreatment with indomethacin did not lead to any difference between the denervated and intact kidney. The results show that renal nerves and prostaglandins participate jointly in the regulation of sodium, copper and calcium excretion. Renal prostaglandins do not change the response of the denervated kidney to furosemide as compared to the intact kidney.     

Dopamine production by the isolated perfused rat kidney

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 +/- 0.1 ng DA X min-1 X g wet weight-1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 +/- 0.06 ng DA X min-1 X g-1 and denervated kidneys excreted 1.0 +/- 0.07 DA X min-1 X g-1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 +/- 0.1 ng DA X min-1 X g-1 (p less than 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng X min-1 X g-1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 +/- 0.13 ng DA X min-1 X g-1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng. kg(-1). min(-1). In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 +/- 4 mmHg and 1.04 +/- 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30-35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 5 Den/Inn sodium = 0.51 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion (day 5 Den/Inn sodium = 2.02 +/- 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.     

Effect of ventilation on sodium excretion in the anesthetized dog with unilateral renal denervation

We studied if the effect of mechanical ventilation induced to keep arterial blood gas values within normal physiological limits has any influence on renal sodium excretion in anesthetized dogs (n = 17) subjected to acute unilateral renal denervation. Compared to the control and the postcontrol periods, ventilation elevated arterial pO2 from 86 +/- 5 to 96 +/- 5 mmHg and blood pH from 7.37 +/- 0.02 to 7.41 +/- 0.01 while arterial pCO2 was decreased from 38 +/- 2 to 33 +/- 1 mmHg (p less than 0.05 in all cases). Compared to the innervated kidney urine flow, urinary sodium and potassium excretion from the denervated kidney were markedly elevated both during spontaneous respiration and during mechanical ventilation but GFR and cPAH were similar on the two sides. Ventilation decreased sodium excretion by the denervated kidney from 314 +/- 26 to 252 +/- 31 mumols/min/100 g k. w. (p less than 0.05). No other excretory changes were noted either in the innervated or in the denervated kidneys. Difference in sodium excretion between innervated and denervated kidneys was decreased from 209 +/- 19 to 126 +/- 20 mumole/min/100 g k. w. (p less than 0.001), due to the ventilation induced diminution of sodium excretion from the denervated kidney. It is concluded that mechanical ventilation of anesthetized dogs modifies sodium excretion, and this phenomenon can be demonstrated only in the denervated kidney.     

Interaction among atrial natriuretic factor (ANF), vasopressin, and renal nerves in terms of renal responses in rats.

The relationship between the renal nerves and vasopressin in terms of the natriuretic and diuretic responses to atrial natriuretic factor (ANF--0.25 microgram/kg/min for 15 min), was investigated in unilaterally denervated anesthetized rats before and after the administration of a vasopressin V2 specific antagonist (AVPX)--(40 micrograms/kg bolus followed by 0.4 microgram/kg/min infusion). Administration of the AVPX or ANF did not alter the arterial pressure. Acute renal denervation or AVPX administration independently produced significant increases in sodium and water excretion. ANF infusion by itself produced a greater increase in urine flow and sodium excretion from the denervated kidney compared to the intact kidney before the administration of AVPX. However, after the administration of AVPX renal responses to ANF from the intact kidneys were enhanced such that they were not significantly different from the denervated kidneys. These results suggest that the full physiological response to ANF may be masked by tonic renal nerve activity or antidiuretic actions of vasopressin. Furthermore, since combined renal denervation and AVPX administration does not produce any greater potentiation of the renal responses to ANF than either of these manipulations alone, it is suggested that they may act via a common mechanism, possibly altering activity in the renal nerves.     

Long-term control of renal blood flow: what is the role of the renal nerves?

We have developed a system for long-term continuous monitoring of cardiovascular parameters in rabbits living in their home cage to assess what role renal sympathetic nerve activity (RSNA) has in regulating renal blood flow (RBF) in daily life. Blood pressure, heart rate, locomotor activity, RSNA, and RBF were recorded continuously for 4 wk. Beginning 4-5 days after surgery a circadian rhythm, dependent on feeding time, was observed. When averaged over all days RBF to the innervated and denervated kidneys was not significantly different. However, control of RBF around these mean levels was dependent on the presence of the renal sympathetic nerves. In particular we observed episodic elevations in heart rate and other parameters associated with activity. In the denervated kidney, during these episodic elevations, the increase in renal resistance was closely related to the increase in arterial pressure. In the innervated kidney the renal resistance response was significantly more variable, indicating an interaction of the sympathetic nervous system. These results indicate that whereas overall levels of RSNA do not set the mean level of RBF the renal vasculature is sensitive to episodic increases in sympathetic nerve activity.     

Effects of vagal neuromodulation and vagotomy on control of food intake and body weight in rats.

Food induced neurohumoral signals are conduced to data processing brain centers mainly as vagal afferent discharge resulting in food intake regulation. The aim of this study was to evaluate effects of vagal nerve neuromodulation in control of food intake with fed-pattern microchip (MC) pacing. Experiments were performed on 60 rats divided on 5 groups: I group 0,05Hz left vagal pacing, II - pacing of both vagal nerves with MC 0,05Hz, III- left vagal MC 0,1Hz pacing, IV - pacing of both vagal nerves with MC 0,1 Hz was performed. In group V left vagal pacing was combined with right side abdominal vagotomy. Body weight and total food intake decreased by 12% and 14% (I), 26% and 30%(II), 8% and 21%(III), 14% and 30%(IV), 38% and 41%(IV), respectively (p<0.05). Effects of both vagal nerves stimulation on final body weight and food intake was significantly more effective than only single nerve MC pacing however most effective was stimulation with 0,1Hz combined with right vagotomy. We conclude that vagal stimulation reduce food intake and body weight by increasing vagal afferent signals. Our results suggest that information in vagal afferents can be modulated resulting in changes of feeding behaviour and body weight.     

Reinvestigation of denervation diuresis and natriuresis in conscious dogs.

The function of innervated and denervated kidney was compared in clearance studies with conscious dogs. The animals were prepared for experiments by unilateral renal denervation and surgical division of the bladder to form two hemibladders enabling separate urine collection from two kidneys. The mean urine flow was 6% higher for the denervated kidney (not significant) while mean differences for osmolar clearance (+ 13%), sodium excretion (+21%) and GFT (+5%) were all significant (P less than 0.05). When corrected to 100 ml GFR, sodium excretion was not significantly higher for the denervated kidney. In most experiments higher sodium excretion on the denefvated side was associated with higher GFR. Thus, contrary to some earlier views, a slight increase in the excretory function which follows denervation of the kidney is demonstrable also in conscious undisturbed animals. The data suggest that increased haemodynamics of the denervated kidney are responsible for higher excretion, but do not exclude a contribution of inhibited tubular reabsorption.     

Role of renal nerves and vasopressin in renal responses to acute volume expansion in rats.

This study was to determine whether the presence or absence of renal nerves and vasopressin altered the diuretic and natriuretic responses to acute volume expansion. Two forms of volume expansion were used: (i) inflation of a small balloon in the veno-atrial junction and (ii) an infusion of isotonic saline at a rate of 1 ml/min for a period of 15 min, approximately 7% of body weight. Balloon inflation produced a significant diuresis from both the intact and denervated kidneys but only produced a significant natriuresis from the intact kidney. Volume expansion (infusion of saline) produced a significant diuresis and natriuresis from both intact and denervated kidneys. Blocking the V2 receptor for vasopressin with a V2-specific receptor blocker d(CH2)5[D-Ile2,Val4]AVP (40 micrograms/kg bolus dose followed by infusion of 4 micrograms/kg/min) did not alter the diuretic and natriuretic responses to volume expansion. However, the absence of renal nerves or the absence of actions of vasopressin produced a significant reduction in the capacity of the kidneys to increase the relative amount of diuresis or natriuresis, thus losing the control over output; i.e., absence of renal nerves only allowed 12-fold increase in diuresis to volume expansion compared with 25-fold in the intact state and absence of vasopressin only allowed 4.6-fold increase in diuresis to volume expansion compared with 25-fold in the intact state. Examining the "volume reflex" in terms of a control system trying to regulate fluid balance, the presence of either renal nerves or actions of vasopressin allows the volume regulating system a greater range in which to control the diuresis and natriuresis (making it possible to fine tune the output to much greater extent).     

Production of urine free dopamine from DOPA; A micropuncture study

The contribution of free L-DOPA to urinary dopamine (D) was examined by microinjecting ³H-DOPA into either proximal tubules or the peritubular space of innervated and denervated rat kidneys. Recirculation of radioactive material was corrected for by comparison with excretion of ¹⁴C inulin included in the injectate. Urine radioactivity was characterized by HPLC. 69.4 ± 2.9% of ³H-DOPA microinjected into proximal tubules appeard in urine from the ipsilateral kidney, 14.6 ± 1.6% of the ³H was recovered as D. After microinjection into the subcapsular peritubular space 4 times as much ³H appeared in the urine from the ipsilateral as from the contralateral kidney. Tubular secretion of total ³H and ³HD was calculated by comparison with ¹⁴C inulin excretion. Chronically denervated kidneys secreted 36.0 ± 4.2% of the microinjected ³H; innervated kidneys secreted 35.0 ± 3.0%. ³H-D secretion was 14.5 ± 3.7% and 15.3 ± 2.8% of the total ³H-DOPA microinjected into denervated and innervated kidneys respectively. We estimated that 30% of the urinary free D is derived from circulating free L-DOPA.     

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of alpha1- and alpha2-adrenoceptors on renal sensory nerve fibers

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating alpha-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the alpha(1)- and alpha(2)-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49 degrees C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 +/- 900 and 4,870 +/- 670%.s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 +/- 210%.s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 +/- 1 to 16 +/- 1 pg/min, and PGE(2) release, from 77 +/- 11 to 161 +/- 23 pg/min, suggesting a role for PGE(2) in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE(2). PGE(2) enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating alpha(1)- and alpha(2)-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE(2).     

牵拉猫左心房所致的肾效应

本实验在50只麻醉猫中研究了牵拉左心房(LAS)对尿量(UV)、尿钠(U_(Na)V)和尿钾(U_KV)排出量的影响。在迷走神经完整的动物,LAS 导致 UV,U_(Na)V 和 U_KV(P<0.001)明显增加。切断迷走神经后 LAS 仍能使 UV,U_(Na)V 有所增加(p<0.01),但增加量明显低于迷走神经完整的动物(P<0.005)。在迷走神经完整的猫滴注肝素(10U/min/mg)后,LAS 也能引起 UV,U_(Na)V 和 U_KV 的增加,但增值明显低于没有滴注肝素的猫。在迷走神经切除后滴入肝素,则 LAS 的肾效应消失(p>0.05)。切断左侧肾神经后,LAS 引起神经完整肾尿量和尿钠排出显著增加(P<0.001)。而去神经肾对 LAS 的效应虽减弱,但其增值仍有显著性。两侧肾效应的差异,在统计学上是显著的(P<0.05)。上述结果说明,LAS 在麻醉猫中能引起尿量,尿钠和尿钾明显增加,这些效应是神经反射和体液机制共同作用的结果。