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.     

Comparison of PGE2, 6-keto PGF1α and renin release from dog kidneys

Several renal cell types synthesize prostaglandin E₂ (PGE₂) and prostacyclin (PGI₂). To examine whether the release of these prostaglandins varies in proportion, prostaglandin synthesis was stimulated in anaesthetized dogs by renal arterial constriction, ureteral occlusion, intrarenal angiotensin II infusion and infusion of arachidonic acid, the precursor of PG synthesis. PGI₂ was measured as its stable hydrolysed product, 6-keto PGF_1α. The two former procedures raised PGE₂ release to 13 ± 2 pmol min^-1, 6-keto PGF_1α release to 5 ± 2 pmol min^-1 and renin release to 23 ± 5 μg AI min^-1, Angiotensin II infusion, reducing the renal blood flow by 30%, increased PGE₂ and 6-keto PGF_1α release only half as much as ureteral and renal arterial constriction, and exerted no significant effect on renin release. By increasing the infusion rate of angiotensin II up to 10 times, the renal blood flow remained unaltered in four dogs and fell to 50% of control in two dogs, but PGE₂ and 6-keto PGF_1α release did not increase further in any of the experiments. Arachidonic acid, infused at 40 and 160 μg kg^-1 min^-1, increased prostaglandin release in proportion to the infusion rate. At the highest infusion rate, PGE₂ release averaged 166± 37 pmol min^-1 and 6-keto PGF_1α release 98 ± 28 pmol min^-1. All procedures increased PGE₂ and 6-keto PGF_1α release in a fixed proportion of about 2.5:1, whereas renin release increased only during autoregulatory vasodilation.     

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.     

The effects of hypothermia on renal function and haemodynamics in the rat

The effects of 1–2 h of hypothermia a t 28d?C and rewarming on renal function were investigated in anaesthetized rats, using conventional clearance methods and the micropuncture technique. Renal blood flow (RBF) decreased from 7.3 ± 0.51 mL min^-1 at 37.5d?C (control) to 4.0 ± 0.47 at 28d?C, with almost complete restoration to 6.9 ± 0.59 mL min^-1 after rewarming. Systemic blood pressure remained essentially unaltered. The RBF reduction seen during hypothermia was due to a 75% increase in vascular resistance, mainly attributable to constriction of the afferent arteriole and increased blood viscosity. This was accompanied by a decline in glomerular capillary pressure from 56.7 ± 0.6 to 46.4 ± 1.3 mmHg, overshooting to 59.0 ± 0.7 mmHg. The glomerular filtration rate (GFR) decreased from 1.1 ± 0.08 to 0.6 ± 0.04 mL min^-l, returning to 1.0 ± 0.07 after rewarming, a pattern also observed for single nephron GFR. This resulted from a decrease in net driving force for glomerular filtration, whereas the filtration coefficient was not affected. Both proximal and distal tubular fluid flow decreased, but fractional reabsorption remained unchanged. In contrast, urine flow increased from 1.8 ± 0.16 to 5.7 ± 1.08 μL min^-1, returning to 2.1 ± 0.18, the increase during hypothermia mainly resulting from a disproportionately reduced fluid reabsorption beyond the mid-distal tubule.     

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.     

Effects of bradykinin and papaverine on renal autoregulation and renin release in the anaesthetized dog

The present study on six anaesthetized dogs investigates the influences of two different vasodilators, bradykinin and papaverine, on the relationship between autoregulation of renal blood flow and glomerular filtration rate, sodium excretion and renin release. At control conditions renal blood flow and glomerular filtration rate was autoregulated to the same levels of renal arterial pressure, 55 ± 3 and 58 ± 3 mmHg, respectively. Renin release increased from 0.3±0.1 to 22±4 μg AI min^-1, and sodium excretion decreased from 99 +29 to 4.6 ± 3.3 μmol min^-1 when renal arterial pressure was reduced from 122±6 to 44±2 mmHg. Infusion of bradykinin (50 ng kg^-1 min^-1) increased renal blood flow by 50% at control blood pressure without changing glomerular filtration rate, and both renal blood flow and glomerular filtration rate autoregulated to the same pressure levels as during control. Sodium excretion increased threefold at control renal arterial pressure, but was unchanged at low renal arterial pressure. Bradykinin did not change renin release neither at control nor low renal arterial pressure. Papaverine infusion at a rate of 4 mg min^-1 increased renal blood flow 50% without changing glomerular filtration rate. The lower pressure limits of renal blood flow and glomerular filtration rate autoregulation were increased to 94±6 and 93±6 mmHg, respectively. Sodium excretion increased sixfold at control renal arterial pressure and was still as high as the initial control values at low renal arterial pressure (97±27 μmol min^-1) accompanied by only a small increase in renin release (1.4±0.3 to 6±2 μg AI min^-1). We conclude that bradykinin does not influence autoregulatory pressure limits of renal blood flow and glomerular filtration rate nor the accompanying increase in renin release during reductions in renal arterial pressure. Papaverine on the other hand maintains high sodium chloride delivery to macula densa at low renal arterial ressure, suppressing renin release and impairing autoregulation through effects on the tubulo-glomerular feedback mechanism.     

Two models of glomerular filtration rate and renal blood flow in the rat

Two mathematical models of glomerular filtration and blood flow are derived. The first is based on principles of fluid and mass conservation in individual capillaries. The model explains why the filtration rate (GFR) is strongly dependent on local hydrostatic and protein oncotic pressures, and on plasma flow rate (GCPF), but only weakly dependent on exact numbers, lengths, radii, or filtration coefficient of glomerular capillaries. The model shows that much of the increased GFR in both isooncotic plasma loading and isotonic Ringer's loading is due to increased GCPF caused by diluting erythrocytes. The second model uses several approximations and reduces to a quadratic in afferent arteriolar blood flow. When arterial pressure, hematocrit, plasma protein concentration, and afferent and efferent arteriolar resistances are specified, the model predicts GFR, afferent arteriolar blood flow, and filtration fraction. Alternatively, if any two of these three variables are known, the model predicts segmental arteriolar resistances. The model indicates that GFR and blood flow regulation must be located in the afferent arteriole, despite the strong dependence of GFR on GCPF.     

Inhibitory effect of endothelin on renin release in dog kidneys

To investigate the effect of endothelin on renin release, experiments were performed in barbiturate-anaesthetized dogs with denervated kidneys. Intrarenal infusion of endothelin (1 ng min^-1kg^-1body wt) reduced renal blood flow (RBF) from 145 ± 10 ml min^-1to 98 ± 9 ml min^-1without altering renin release (1 ± 1 μg angiotensin I (AI) min^-1). Renin release was then increased either by renal arterial constriction or ureteral occlusion. When renal arterial pressure was reduced to 50 mmHg, renin release averaged 79 ± 20 μg AI min^-1in six dogs and fell significantly to 24 ± 6 μg AI min^-1during endothelin infusion. During ureteral occlusion the inhibitory effect of endothelin on renin release either during inhibition of β-adrenergic activity with propranolol or after inhibiting prostaglandin synthesis by indomethacin during intrarenal infusion of isoproterenol was examined. After propranolol administration ureteral occlusion increased renin release from 5 ± 2 μg AI min^-1to 38 ± 12 μg AI min^-1in six dogs. Subsequent intrarenal endothelin infusion (1 ng min^-1kg^-1body wt) during maintained ureteral occlusion reduced renin release to 10 ± 3 μg AI min^-1. In six other dogs prostaglandin synthesis was inhibited by indomethacin. Subsequent infusion of isoproterenol (0.2 μg min^-1kg^-1body wt) to stimulate β-adrenoceptor activity increased renin release from 13 ± 4 μg AI min^-1to 68 ± 8 μg AI min^-1during ureteral occlusion. Intrarenal endothelin infusion (1 ng min^-1kg^-1body wt) reduced renin release to 22 ± 3 μg AI min^-1during continuous isoproterenol infusion and ureteral occlusion. Hence endothelin inhibits renin release induced by renal arterial constriction or ureteral occlusion. Similar inhibitory effects whether renin release was raised by increasing prostaglandin synthesis or by stimulating β-adrenergic activity suggest a direct effect of endothelin on the juxtaglomerular cells.     

Bradykinin-induced renal hemodynamic alterations: renin and prostaglandin relationships

The present studies examined the role of the renin-angiotensin system as a modifier of the renal vasomotor response to bradykinin. Renal arterial bradykinin infusion (80 ng.kg-1.min-1) initially resulted in increased renal blood flow (RBF). The secretory rates of renin and prostaglandins increased after 60 min. With continued bradykinin administration (120 min) RBF and prostaglandin secretory rates returned toward control values, although renin secretory rate remained elevated (P less than 0.02). After prostaglandin synthetase inhibition, RBF decreased and bradykinin administration returned RBF to control values. Prostaglandin secretory rates decreased after meclofenamate (P less than 0.005). Continued bradykinin infusion resulted in a return of the renin secretory rate to control values. The administration of bradykinin after competitive inhibition of angiotensin II resulted in a sustained increase in renal blood flow. These results suggest that the initial bradykinin-induced renal hyperemia is only partially dependent on enhanced prostaglandin release, the increase in renin secretion by bradykinin infusion after prostaglandin synthetase inhibition is consistent with a bradykinin and renin interaction, and the lack of a sustained hyperemia after bradykinin is related to increased renin-angiotensin system activity.     

Role of glomerular prostanoid in control of glomerular filtration rate in rats

Summary It is generally accepted that the main action of glomerular prostanoids (GPs) on glomerular filtration rate (GFR) is to modulate the activity of different vasoconstrictors, specially in states of renal hypoperfusion. However it was also suggested that GPs may directly affect GFR. The present study was focused on this last hypothesis, in different experimental models, in rats.In adriamycin induced acute renal failure, the transient decrease of GFR is associated with higher levels of thromboxane B₂. Later on, when GFR returns to normal, vasodilator prostaglandins synthesis was also increased.In captopril induced renal failure in Na depleted rats (where GPs synthesis remained normal), stimulation of PGE₂ and PGI₂ production by K and NaCl was associated with a significant improvement of GFR. Furthermore, the increase in GFR induce by NaCl was prevented by inhibition of prostaglandin synthesis.Infusion of atrial natriuretic peptide in euvolemic rats induce a marked elevation both of GFR and PGE₂ synthesis. It was abolished by previous administration of prostaglandin synthesis inhibitor.In conclusion, glomerular prostanoids may influence GFR, either directly, or as mediator or modulator of other vasoactive hormones.Abbreviations GPs glomerular prostanoids - PG prostaglandin - TX thromboxane - ANP atrial natriuretic peptide - GFR glomerular filtration rate - PE polyethylene Nachtrag zu den Hauptreferaten des 19. Kongresses der Gesellschaft für Nephrologie in Göttingen (Klin Wochenschr 66/18)     

Hemodynamic mechanisms influencing sodium excretion during angiotensin infusion.

To examine mechanisms of transition between antinatriuresis and natriuresis, angiotensin II was first infused intrarenally (0.001-0.07 mug/kg-min) in anesthetized dogs; glomerular filtration rate (GFR), sodium excretion, and intrarenal pressure (IRP), indicating tubular pressure, fell as during mechanical aortic constriction. During supplementary intravenous infusion (0.10-0.30 mug/kg-min), renal blood flow (RBF) rose toward control (tachyphylaxis). Tubular reabsorption increased but was still 17.1% below control. Filtration fraction averaging 0.31 remained constant. Sodium excretion and IRP exceeded control but were normalized by restoring renal arterial pressure mechanically. During intrarenal angiotensin infusion, carotid constriction increased blood pressure more, but RBF, IRP, and sodium excretion less than intravenous angiotensin. Intrarenal infusion of angiotensin at 0.10-0.20 mug/kg-min increased RBF and sodium excretion more in infused than in contralateral kidneys. Thus, angiotensin natriuresis depends on increased perfusion pressure and is augmented as tachyphylaxis develops. High correlation between sodium excretion and IRP at unchanged filtration fraction suggests a regulation of sodium excretion by hydrostatic rather than oncotic pressures in glomerular and peritubular capillaries.     

Effect of atrial natriuretic factor on renal prostaglandin E2 release in the anaesthetized dog

Experiments were undertaken in two groups of barbiturate anaesthetized dogs to examine whether atrial natriuretic factor (ANF) exerts an effect on renal release of prostaglandin E₂ (PGE₂). In the first group, intravenous infusion of ANF (50 ng min^-1kg^-1body wt) reduced basal PGE₂ release from 4.4 ± 0.8 pmol min^-1to 1.8 ± 0.7 pmol min^-1. In the second group, intrarenal infusion of an α-adrenoceptor agonist, phenylephrine (2.5–6.75 μg min^-1), raised PGE₂ release from 2.7 ± 0.5 pmol min^-1to 7.5 ± 1.3 pmol min^-1. During continuous α₁-adrenergic stimulation, intravenous infusion of ANF (100 ng min^-1kg^-1body wt) reduced PGE₂ release to 3.5 ± 1.0 pmol min^-1. These results demonstrate that ANF reduces basal and α₁-adrenergic stimulated renal PGE₂ release.     

The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog

It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i. v. bolus of 0.1 mg/kg ramiprilat followed by an infusion of 5 μg kg⁻¹ min⁻¹. Subgroups each comprising six dogs were also treated with either HOE-140, a bradykinin B₂ receptor antagonist, or the cyclooxygenase inhibitor indomethacin. In general, renal effects of ramiprilat were more pronounced in dogs fed on low salt than in those on normal diet. In dogs on low salt, the mean arterial pressure decreased by 20% 20 min after ramiprilat application, whereas the total renal blood flow rose by 71% from 4.71 to 8.06 ml min⁻¹ g kidney weight⁻¹ and the glomerular filtration rate (GFR) by 28% from 0.74 to 0.95 ml min⁻¹ g⁻¹. Single-nephron glomerular blood flow and single-nephron GFR rose by 55% and 23% respectively. The total and the single-nephron filtration fraction decreased by 25% and 23% respectively. There were no substantial changes in glomerular and peritubular capillary and tubular pressures, but a significant increase in the ultrafiltration coefficient, K _f, by 103% from 3.55 nl/ mmHg to 7.19 nl/mmHg (26.7–54.0 nl/kPa) was observed. Afferent and efferent arteriolar resistances decreased in parallel by 55% and 47%. Prior and concomitant intrarenal arterial infusion of HOE-140 at a dose that blocked the vasodilatory effect of 9 ng kg⁻¹ min⁻¹ bradykinin had no significant effects in dogs on low salt but attenuated the relative rise in renal and single-nephron glomerular blood flow and K _f by 21%, 27% and 26% respectively in dogs on low salt (P<0.01). No such effects were observed with indomethacin. We conclude that ACE inhibition in the dog results in a parallel decrease in afferent and efferent resistance and significantly increases K _f. This latter effect is partly mediated by the kinin system under conditions of Na⁺ depletion.     

Effect of an angiotensin II antagonist on autoregulation in the isolated dog kidney.

The effect of the specific angiotensin II antagonist (AIIA), [1-sarcosine-8-alanine]angiotensin II, on autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in an isolated dog kidney was examined. Infusing the AIIA into the renal artery at 1.9 mug/min inhibited the renal vasoconstrictor action of angiotension II infused simultaneously at 1.15 mug/min. Under conditions of constant renal arterial pressure the AIIA had no significant effect on sodium excretion, GFR, RBF, cortical blood flow distribution (microsphere method), or renin secretion in non-renin-depleted kidneys. Similarly, no agonist properties were observed when the AIIA was infused into renin-depleted kidneys. This dose of the AIIA did not impair the capacity of the isolated kidney to regulate GFR or RBF when renal arterial pressure was increased from 100 to 150 mmHg. Efficiency of autoregulation of GFR and RBF was 77 and 82% of that predicted for perfect autoregulation. These values are not significantly different from those of the isolated kidney not infused with the antagonist. It is concluded that the angiotensin II antagonist, [1-sarcosine-8-alanine]angiotensin II, has no significant agonist properties, that it antagonizes the renal vascular effects of exogenously administered angiotensin II, but does not impair renal autoregulation. These data provide no support for the hypothesis that the renin-angiotensin system mediates the autoregulation of GFR and RBF.     

Comparison of PGE2, 6-keto PGF1 alpha and renin release from dog kidneys

Several renal cell types synthesize prostaglandin E2 (PGE2) and prostacyclin (PGI2). To examine whether the release of these prostaglandins varies in proportion, prostaglandin synthesis was stimulated in anaesthetized dogs by renal arterial constriction, ureteral occlusion, intrarenal angiotensin II infusion and infusion of arachidonic acid, the precursor of PG synthesis. PGI2 was measured as its stable hydrolysed product, 6-keto PGF1 alpha. The two former procedures raised PGE2 release to 13 +/- 2 pmol min-1, 6-keto PGF1 alpha release to 5 +/- 2 pmol min-1 and renin release to 23 +/- 5 micrograms AI min-1. Angiotensin II infusion, reducing the renal blood flow by 30%, increased PGE2 and 6-keto PGF1 alpha release only half as much as ureteral and renal arterial constriction, and exerted no significant effect on renin release. By increasing the infusion rate of angiotensin II up to 10 times, the renal blood flow remained unaltered in four dogs and fell to 50% of control in two dogs, but PGE2 and 6-keto PGF1 alpha release did not increase further in any of the experiments. Arachidonic acid, infused at 40 and 160 micrograms kg-1 min-1, increased prostaglandin release in proportion to the infusion rate. At the highest infusion rate, PGE2 release averaged 166 +/- 37 pmol min-1 and 6-keto PGF1 alpha release 98 +/- 28 pmol min-1. All procedures increased PGE2 and 6-keto PGF1 alpha release in a fixed proportion of about 2.5:1, whereas renin release increased only during autoregulatory vasodilation.     

Local intrarenal vasoconstrictor-vasodilator interactions in mild partial ureteral obstruction.

Micropuncture studies were performed in Munich-Wistar rats with surgically created chronic partial unilateral ureteral obstruction (UUO). Mean values for superficial single nephron (SN)GFR, total GFR, and initial glomerular plasma flow rate (QA) in obstructed kidneys were essentially identical to values in nonobstructed kidneys. Nevertheless, glomerular capillary hydraulic pressure (PGC) was significantly higher in obstructed than in nonobstructed kidneys. This increase in PGC served to offset the markedly reduced glomerular capillary ultrafiltration coefficient that was also confined to the kidneys ipsilateral to the ureteral obstruction. During infusion of indomethacin or meclofenamate, SNGFR and QA decreased significantly, in association with elevations in arteriolar resistances in obstructed kidneys, whereas such changes were not observed in nonobstructed kidneys. The results suggest that local intrarenal factors, rather than circulating or systemic factor(s), bring about functional adaptations to partial ureteral obstruction. In particular, an indomethacin- and meclofenamate-sensitive vasodilator (presumably prostaglandin) plays a role in antagonizing the effects of a simultaneously acting vasoconstrictor which, although not identified, displayed the functional properties of angiotensin II.     

Resetting of renal autoregulation in conscious dogs: angiotensin II and alpha1-adrenoceptors

It has recently been shown, that common carotid occlusion (CCO) impairs autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). This study was designed to investigate the mechanisms by which a moderate sympathetic stimulus influences RBF and GFR autoregulation. CCO provided a moderate sympathetic stimulus, and impaired autoregulation by increasing the lower autoregulatory limit of RBF and GFR by 21–30 mmHg. Basal RBF and GFR were not affected. A low-dose intrarenal infusion of the ₁-adrenoceptor agonist methoxamine (which did not change total RBF or GFR) induced a similar shift as CCO (n=5, RBF: +31±11 mmHg, P<0.05; GFR: +24±4 mmHg, P<0.01). In another group it was shown, that a combination of CCO with an intrarenal angiotensin II (A II) blockade (saralasin) did not significantly alter the response to CCO (n=7). These data suggest an ₁-adrenergic pathway for the sympathetic resetting of autoregulation. An augmented A II formation does not play a major role in mediating this effect.     

花生四烯酸氧化产物对肾毒性肾炎肾脏血液动力学的影响

应用血栓素合成抑制剂、５－脂氧化酶抑制剂及１２－脂氧化酶抑制剂对肾毒性肾炎大鼠进行预处理，测定其肾小球滤过率、肾血流量及肾小球合成的前列腺素Ｅ２、血栓素Ｂ２、白三烯Ｂ４及１２－羟二十碳四烯酸。发现这三种抑制剂分别抑制制肾小球合成血栓素Ｂ２、白三烯Ｂ４及１２－羟二十碳四烯酸，并缓解了肾小球滤过率及肾血流量的下降程度。由此证实以上三种物质参与肾毒性肾炎中的肾脏血液动力学紊乱。     

The effect of two different calcium antagonists on the glomerular haemodynamics in the dog

Kidney function of beagles fed a constant amount of food containing 3 mmol sodium.kgbodywt⁻¹.day⁻¹, and anaesthetized with pentobarbitone was investigated by clearance and micropuncture techniques during an intrarenal infusion of saline or the calcium antagonists verapamil (VER, 4 μg.kgbodywt⁻¹.min⁻¹) or nifedipine (NIF, 0.3 μg.kgbodywt⁻¹.min⁻¹). Neither drug changed the mean arterial pressure. Apart from the natriuresis and diuresis, which were significantly greater with NIF than with VER, the response to both drugs was similar. Increases in renal blood flow (RBF; 17% with VER, 20% with NIF), glomerular filtration rate (GFR; VER: 34%; NIF: 39%) and filtration fraction (VER: 12%; NIF: 14%) were observed; similar values were obtained at the single nephron level. Pressure in glomerular capillaries, measured directly after ablation of a thin layer of cortex corticis, was increased by 11% with VER and 10% with NIF; no changes in proximal tubular and peritubular capillary pressure were seen. The glomerular ultrafiltration coefficient (K_f) did not change with either drug. Total arteriolar resistance was decreased (VER: 20%; NIF: 15%) due to a decrease in afferent resistance (VER: 31%; NIF: 27%) with no corresponding change in efferent resistance. The cause of the lack of responsiveness of the efferent arteriole remains unclear. In conclusion, in acute experiments with intrarenal administration, both drugs increase RBF and GFR by a preferential afferent dilatory mechanism without any change in K_f.     

Effect of isotonic volume expansion on glomerular filtration rate and renal hemodynamics in the developing rat kidney

Young rats (20–24 days) and adult rats (4–5 days) were studied during hydropenia and volume expansion with regard to glomerular filtration rate (GFR) and the determinants of GFR. During hydropenia, GFR and renal blood flow (RBF) were significantly lower in younger than in adult rats both in absolute terms and when related to bodyweight. Equivalent degrees of volume expansion (6% of b. wt.) resulted in a much more pronounced increase in GFR and RBF in younger than in older rats. This suggests that the high renal vascular resistance in hydropenic young rats is primarily due to vasoconstriction. The relationship between the filtration rate of superficial nephrons and the total GFR was the same in hydropenic and volume expanded rats in both age groups. The tubular stop flow pressure, the calculated hydrostatic glomerular capillary pressure and ultrafiltration pressure in the afferent part of the glomerular capillaries was slightly lower in hydropenic young rats than in hydropenic adult rats. The pressures did not rise after volume expansion. It is concluded that the marked increase in GFR in volume expanded young rats is mainly due to increased renal plasma flow.