Effect of vasoactive agents on the distribution of renal cortical blood flow in dogs.

The distribution of renal cortical blood flow was studied in 6 Nembutal anesthetized dogs during control periods and during infusions of adrenaline, noradrenaline, angiotensin and vasopressin. Local cortical blood flow was measured as H2 gas desaturation rate recorded polarographically by platinum electrodes in outer and inner cortex. The total renal blood flow (RBF) was measured by an electromagnetic flow meter. In the control period the outer cortical blood flow (OCF) and inner cortical blood flow (ICF) averaged 3.59 (+/- S.D. 0.85) ml/min - g and 3.23 (+/- S.D. 0.64) ml/min - g, respectively. Infusions of the various vasoactive agents caused essentially equal vascular responses. All agents caused increased local renal resistance and reduction of RBF whether given intravenously or intraarterially. The RBF could be lowered to 20-50% of initial control flow by increasing doses of vasoactive agents. OCF and ICF fell proportionately and almost to the same extent as RBF, or OCF fell slightly more than ICF. There was no evidence for patchy or zonal hypoperfusion in cortex caused by infusion of adrenaline, noradrenaline, angiotensin and vasopressin.     

Blood flow heterogeneity in the renal cortex during burn shock in dogs

Blood flow distribution and occurrence of intermittent, patchy ischaemia in the renal cortex were investigated in anaesthetized dogs before and during burn shock. Severe or moderate thermal injury was induced by scalding 30% of body surface by 90 degrees C or 70 degrees C hot water. Local blood flow in outer and inner cortex was measured by microspheres and by electrodes recording hydrogen gas washout rates. The haematocrit rose much more in the moderately than in the severely scalded dogs, due to marked haemolysis in the latter group. Cortical blood flow was reduced more after severe than after moderate thermal injury. A significant redistribution of blood flow from outer to inner cortex was not demonstrated. Abrupt shifts in local washout rates were observed in most dogs during shock, but was consistently more frequent in the moderately scalded dogs. Such episodes of patchy intermittent ischaemia were not seen after inhibition of prostaglandin synthesis by indomethacin. Thus, prostaglandins may mediate focal vasoconstriction in the renal cortex during burn shock in dogs.     

The effect of prostaglandin synthesis inhibitors on renal blood flow distribution in conscious rabbits.

1. We have studied the effects of two prostaglandin synthesis inhibitors on renal cortical blood flow distribution in conscious rabbits. 2. Renal blood flow distribution was estimated by means of radioactive microspheres injected into chronically implanted left atrial cannulae. Cardiac output was measured by a thermodilution technique. 3. Measurements were made in groups of animals treated with either indomethacin, meclofenamate or control injections of phosphate buffer. 4. A method of microtome slicing of the renal cortex was developed to standardize measurements. Microtome sections were grouped into inner, middle and outer zones. After both indomethacin and meclofenamate there was a reduction in total renal blood flow with a redistribution of flow from inner to outer cortex. 5. Estimated renal vascular resistance rose in all three cortical zones. 6. The data support the hypothesis that renal prostaglandin synthesis is necessary for maintaining flow to the deep cortex. It is suggested that renal prostaglandins may also influence flow in more superficial zones. 7. Estimated total systemic vascular resistance was increased both with meclofenamate and indomethacin, suggesting an inhibiting effect of prostaglandins on arteriolar tone throughout a major part of the systemic circulartion.     

Renal blood flow distribution during E. coli endotoxin shock in dog

The effect of endotoxin on renal blood flow distribution was studied in anesthetized dogs. Renal blood flow was measured as hydrogen clearance by platinum electrodes placed in outer and in inner halves of cortex and by electromagnetic flowmeter. Intravenous injection of E. coli endotoxin, 3–5 mg/kg b. wt., promptly reduced arterial blood pressure (AP) and renal blood flow. After a transient increase for 45 min AP and renal blood flow declined to about 50% of the control 2½-3 h after injection. The reduction in outer cortical blood flow (OCF) was not significantly different from the reduction in inner cortical blood flow (ICF). The hematocrit (Hct) increased from 40.1±3.8% to 54.6±8%, but mean renal vascular resistance did not change. Total plasma protein concentration was not significantly elevated. A marked local flow variability was observed in some periods during the phase of shock with declining AP and total renal blood flow at high Hct. Thus renal blood flow showed phasic changes, but the OCF/ICF ratio was not changed during endotoxin shock. Local blood flow instability was observed periodically at high Hct.     

Renal Cortical Blood Redistribution after Bumetanide Related to Heterogenicity of Cortical Prostaglandin Metabolism in Dogs

Bumetanide is shown to increase renal blood flow and to augment the proportion of the cortical blood flow to middle cortex. This redistribution still takes place even when renal blood flow is maintained constant by renal artery clamping. Indomethacin pretreatment inhibits the increase of renal blood flow as well as the cortical blood redistribution. In vitro examinations of canine kidney tissue slices suggest that outer cortex and papilla are sites of prostaglandin synthesis. No differences in prostaglandin E degradation are observed within the cortex. This suggests a relative autonomy for prostaglandins in the outer cortex, whilst inner cortical areas are dependent on medullary/papillary prostaglandin E supply. The renal hemodynamic effect of bumetanide is therefore thought to be a result of a stimulation of mainly medullary/papillary prostaglandin synthesis.     

Prostaglandins but not nitric oxide protect renal medullary perfusion in anaesthetised rats receiving angiotensin II

Angiotensin II (Ang II) fails to constrict renal medullary vasculature, possibly due to the counteraction of local vasodilators, such as prostaglandins or nitric oxide (NO). The effects of exogenous Ang II on intrarenal circulation were determined in anaesthetised rats that were untreated or pretreated with indomethacin (Indo) or l -NAME. The total renal blood flow (RBF), representing cortical perfusion, and outer and inner medullary blood flow (OMBF and IMBF) were measured. In untreated rats, Ang II decreased RBF in a dose dependent manner. Intravenous administration of 30 ng kg⁻¹ min⁻¹ Ang II decreased RBF by 38 % and OMBF by 9 % (both significant); IMBF was unaffected. Indo (5 mg kg⁻¹ i.v. ) significantly and similarly decreased OMBF and IMBF without affecting RBF. Ang II decreased IMBF by 27 % in Indo-pretreated rats, but caused no change in rats without pretreatment. The decreases in OMBF and RBF were comparable with or without Indo pretreatment. Inhibition of NO synthesis with l -NAME (0.6 mg kg⁻¹ i.v. ) significantly decreased RBF, OMBF and IMBF. Ang II infusion into l -NAME-pretreated rats induced a further significant decrease in RBF and OMBF without changing IMBF. We conclude that within the inner medulla, but not the outer medulla or cortex, prostaglandins effectively counteract the vasopressor effect of circulating Ang II.     

Renal cortical blood flow distribution measured by hydrogen clearance during dopamine and acetylcholine infusion. Effect of electrode thickness and position in cortex.

Blood flow distribution in the renal cortex was investigated in control and during i.a. infusion of dopamine (DA) and acetylcholine (Ach) in dogs. Local blood flow in outer cortex (OCF) and in inner cortex (ICF) was measured by platinum electrodes detecting hydrogen washout rate in tissue. Mean cortical blood flow measured by hydrogen washout rate in the renal vein (CFV) was compared with renal arterial blood flow (RAF) measured by electromagnetic flowmeter. With electrodes of 0.05-0.2 mm diameter control blood flow rates in outer and inner cortex were 4.57 +/- (S.D.) 1.73 ml/min.g, and 4.35 +/- 0.57 ml/min.g, which is higher than found using 0.2-0.5 mm electrodes in this and previous studies. OCF and ICF increased proportionally during intraarterial infusion of DA or Ach. The increase in local blood flow per unit volume was about 20% less than the increase in RAF, most likely due to an increase in renal volume and a reduced vasodilatory response in the surrounding of some electrodes. CFV rose almost to the same degree as RAF, showing a diffusion equilibrium for hydrogen gas even at maximal flow rate. During vasoconstriction induced by high doses of DA, OCF and ICF fell proportionately. Thus, equal vascular responses in outer and inner cortex were observed during both vasodilator and vasoconstrictor infusion. This indicates that changes in sodium excretion with renal blood flow may not be associated with a redistribution of cortical peritubular blood flow.     

Renal cortical blood flow distribution measured by hydrogen clearance during dopamine and acetylcholine infusion. Effect of electrode thickness and position in cortex

Blood flow distribution in the renal cortex was investigated in control and during i.a. infusion of dopamine (DA) and acetylcholine (Ach) in dogs. Local blood flow in outer cortex (OCF) and in inner cortex (ICF) was measured by platinum electrodes detecting hydrogen washout rate in tissue. Mean cortical blood flow measured by hydrogen washout rate in the renal vein (CFV) was compared with renal arterial blood flow (RAF) measured by electromagnetic flowmeter. With electrodes of 0.05–0.2 mm diameter control blood flow rates in outer and inner cortex were 4.57± (S.D.) 1.73 ml/min g and 4.35±0.57 ml/min g, which is higher than found using 0.2–0.5 mm electrodes in this and previous studies. OCF and ICF increased proportionally during intraarterial infusion of DA or Ach. The increase in local blood flow per unit volume was about 20% less than the increase in RAF, most likely due to an increase in renal volume and a reduced vasodilatory response in the surrounding of some electrodes. CFV rose almost to the same degree as RAF, showing a diffusion equilibrium for hydrogen gas even at maximal flow rate. During vasoconstriction induced by high doses of DA, OCF and ICF fell proportionately. Thus, equal vascular responses in outer and inner cortex were observed during both vasodilator and vasoconstrictor infusion. This indicates that changes in sodium excretion with renal blood flow may not be associated with a redistribution of cortical peritubular blood flow.     

Effects of renal nerve stimulation on intrarenal blood flow in rats with intact or inactivated NO synthases

AIM: We studied a possible action of nitric oxide (NO), an intrarenal vasodilator, to buffer a decrease in renal perfusion induced by electrical stimulation of renal nerves (RNS). METHODS: In anaesthetized rats RNS was performed (15 V, 2 ms pulse duration) for 10 s at the frequencies of 2, 3.5, 5 and 7.5 Hz. The total renal blood flow (RBF), an index of cortical perfusion, was measured using a Transonic probe on the renal artery. The outer and inner medullary blood flow (OMBF, IMBF) was measured by laser-Doppler flowmetry. The effect of RNS on RBF, OMBF and IMBF was determined in rats which were either untreated or pre-treated with L-NAME (0.6 or 1.8 mg kg(-1) i.v.), or S-methyl thiocitrulline (SMTC, 20 microg kg(-1) min(-1) i.v.), a selective inhibitor of neuronal NO synthase (nNOS). RESULTS: In untreated rats, RNS decreased IMBF significantly less than RBF and OMBF. High-dose L-NAME treatment significantly enhanced the RNS induced decrease of RBF but not of OMBF or IMBF. SMTC treatment significantly enhanced the decrease of IMBF, without affecting the response of RBF or OMBF. CONCLUSION: At intact NO synthesis the inner medullary circulation is not controlled by renal nerves to the extent observed for the outer medulla or cortex. NO generated by all NOS isoforms present in the kidney buffers partly the intrarenal vasoconstriction triggered by electrical RNS. The NO derived from nNOS seems of particular importance in the control of inner medullary perfusion, interacting with NO generated by endothelial NOS and renal nerves.     

Effect of hemorrhagic shock on renal release of prostaglandin E.

The effect of hemorrhage and reinfusion on renal release of prostaglandin E (PGE), arterial [PGE], mixed-venous [PGE], and renal function was observed in anesthetized dogs. Following hemorrhage to 60 mmHg arterial pressure, arterial [PGE] rose significantly from 405 to 740 pg/ml. Renal release of PGE remained near control (8 ng/min), as renal blood flow (RBF) decreased from 4.7 to 2.2 ng/min per gram kidney weight (KW). Mixed-venous [PGE] remained near the control value (960 pg/ml). Reinfusion of shed blood restored RBF to 4.0 ml/min per KW. Renal release of PGE rose significantly to 190 ng/min. Arterial [PGE] remained elevated, but mixed-venous [PGE] was not significantly different from control. Indomethacin, a prostaglandin synthesis inhibitor, caused a significant decrease in renal release of PGE. Arterial [PGE] remained elevated following treatment. The inhibition of PGE release from the kidney by indomethacin indicates that increased renal release of PGE following reinfusion is the result of accelerated PGE synthesis. The data suggest that the elevated arterial [PGE] may be the result of alteration of the handling of PGE by the lung.     

Total and regional renal blood flow during complete unilateral ureteral obstruction

Regional renal blood flow was investigated after 1, 2, 12 and 24 h of unilateral ureteral obstruction in rats. Total renal and cortical blood flow rates were determined by the microsphere technique and regional medullary blood flow by the 86-Rb extraction method. The kidneys were microdissected into cortex and medulla, which was further divided into the outer stripe and the inner stripe of the outer zone, and the inner zone. In the obstructed kidneys cortical blood flow increased by 33% after 1 h of obstruction, but was normalized after 2 h. After 12 and 24 h this flow was significantly decreased (55% and 65% of control respectively). The pattern of total renal blood flow was similar to that of cortical blood flow. In the outer stripe there was an initial increase (44%) after 1 h, but later no significant deviations from control values were found. After 1 h of obstruction the blood flows in the inner stripe and the inner zone were not significantly different from control values. A significantly decreased blood flow was seen in the inner stripe after 2 h (57% of control) and in the inner zone after 12 h (58% of control). A significant recovery of the blood flow had occurred in the inner stripe and the inner zone after 24 h of obstruction. In the contralateral, non-obstructed kidney no significant changes were found, besides an increased innerstripe blood flow after 24 h of UUO.     

The pressure-flow relationship of different nephron populations in the rat.

The mechanisms behind the autoregulation of the total renal blood flow and the glomerular filtration rate are unclear. In this investigation a modified microsphere technique was applied to measure the blood flow at different depths in the renal cortex during normotensive and hypotensive conditions. No autoregulation was found in the outer cortex while it was well pronounced in the inner one. During similar conditions, glomerular capillary pressure, welling point pressure and intratubular pressure were recorded. By combining these results with the blood flow data, the preglomerular and postglomerular resistances were calculated. It was then found that the preglomerular resistance decreased and the postglomerular resistance increased when the blood pressure was lowered. The results indicate a redistribution of blood flow from the outer parts to the inner parts of the cortex when the blood pressure is decreased. The redistribution of the blood flow might explain the well known linear relationship between the arterial pressure and the urine flow. The single nephron filtration rate of the outermost glomeruli could be calculated and the results seem to indicate a non-equilibrium at the end of the glomerular capillaries.     

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.     

Effects of steady-state plasma vasopressin levels on the distribution of intrarenal blood flow on electrolyte excretion.

1. In order to evaluate the effects of arginine vasopressin (AVP) on the distribution of intrarenal blood flow and on electrolyte excretion, steady-state plasma AVP levels (4-8, 19-1, 44-3, and 100-6 micro u./ml.) were produced in anaesthetized dogs, which were hydrated to minimize endogenous anti-diuretic hormone (ADH) release. 2. The urinary excretion of sodium and potassium increased without change in their filtered loads during AVP infusion. 3. Measurement by the 133xenon washout method revealed diphasic blood flow shifts, as a function of the plasma AVP level, between compartment 1 (outer cortex) and compartment 2 (inner cortex and outer medulla) without change in compartment 3 (inner medulla). 4. In a separate study, the radioactive microsphere (15 micronm) method was used with a plasma AVP levels of 19-8 micronu./ml. Blood flow (expressed as % flow/g tissue) decreased in the outer cortex and increased in the inner cortex. 5. Total renal blood flow did not change during infusion of AVP. However, the values measured by 133xenon were lower than those measured by the microsphere method. 6. There was agreement between these two independent methods that blood flow shifted from outer to inner cortex, with no change in total renal flow, at similar plasma AVP levels (19-1 and 19-8 micronu./ml.). The relationship of these intrarenal circulatory changes to the increased electrolyte excretion is discussed.     

Renal blood flow distribution at varying perfusion pressure in the alloperfused dog kidney

Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 m in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.0 kPa (130, 95 and 60 mm Hg) in isolated alloperfused dog kidneys. Renal blood flow (RBF) was never interrupted during the isolation. Experiments with M showed a marked inequality of the tissue blood flow in different parts of the renal cortex at a constant PP of 17.3 kPa. TBF was highest in the outermost quarter and lowest in the juxtamedullary one. Using CRBC, a homogeneous TBF was observed in the outer 3/4 of the renal cortex with a lower flow in the innermost quarter. With M, a typical percent redistribution of TBF and GBF into the inner cortical regions was indicated during PP reduction. With CRBC, this phenomenon was observed only at PP below the range of RBF autoregulation (8.0 kPa) and was much less conspicuous than with M. The smaller size and higher elasticity of CRBC as compared with M, may result in a more realistic reflection of cortical blood flow distribution. The GBF of outermost superficial glomeruli decreases, even with CRBC, with each PP reduction, the difference exhibiting only a 5% significance level. The lower limit of BF autoregulation in these glomeruli seems to be some-what higher than that of total RBF autoregulation.     

Mechanism of intrarenal blood flow redistribution after carotid artery occlusion.

Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.     

Renal effect of meclofenamate in presence and absence of superfusion bioassay.

Systemic blood pressure (SBP), renal blood flow (RBF), renal vascular resistance (RVR), and arterial and renal venous prostaglandin E (PGE) concentrations were determined in pentobarbital-anesthetized dogs.The effect of sodium meclofenamate infused into the renal artery was compared under two sets of conditions. In experiments carried out under control conditions, SBP, RBF, and RVR were stable and meclofenamate caused only a slight decrease in RBF (5.4%) and increase in RVR.     

Effect of Dehydration on Renal Blood Flow in Dog

The effect of dehydration on intrarenal blood flow was investigated in 11 dogs, using polarographic determination of H₂-gas desaturation for measuring local blood flow in inner cortex (ICF) and outer cortex (OCF). Dehydration was induced by 48 h water deprivation + 2–300 mg ethacrynic acid (EA) per os the day before the experiment. Compared to a control group (n = 9) ICF was markedly reduced to 2.40 ± 0.47 ml/min×g (control 3.23 ± 0.64) whereas OCF 3.29 ± 0.80 ml/min×g was nearly unchanged (control 3.59±0.85). The ratio OCF/ICF was increased to 1.37 (1.11). Further dehydration by hypertonic peritoneal dialysis for 3 h increased Hct to 60 ± 4 and further reduced OCF and ICF, without significant change of the OCF/ICF-ratio. At Hct above 55 sudden and intermittent changes in local cortical blood flow were recorded randomly at individual electrode sites, showing ischemic periods lasting for 1 to 60 min. Such flow changes were observed in 13 of 14 expts. and were not accompanied by changes in RBF. It is concluded that moderate dehydration causes a greater reduction of ICF than of OCF. Severe dehydration gives in addition rise to patchy, intermittent ischemia in both cortical layers.     

Influence of indomethacin and of prostaglandin E1 on total and regional blood flow in man

The central and regional circulatory effects in man of the prostaglandin synthetase inhibitor indomethacin and of prostaglandin E1 (PGE1) were studied. Systemic blood pressure, cardiac output, and renal and splanchnic blood flow were measured at rest, following infusion of indomethacin (50 mg i.v.), and during infusion of PGE1 (4--8 mg x min-1 i.v.) after the administration of indomethacin. An increase in the total systemic resistance (+ 20%), as well as in the renal (+ 30%) and splanchnic (+ 16%) vascular resistances developed rapidly following the administration of indomethacin. Infusion of PGE1 completely restored the resistance in the renal and splanchnic regions, and in addition markedly increased the blood flow in non-visceral tissues. We suggest that the circulatory effects by indomethacin are elicited via the drug's inhibitory effect on prostaglandin synthetase in the vessel walls, and that vasodilating products of PG synthetase affect the regional blood flow distribution in man.     

The effect of prostaglandin inhibition on renal function in the developing anesthetized lamb

The importance of prostaglandin (PG) compounds for renal function in the developing kidney was studied by comparing renal blood flow (RBF), glomerular filtration rate (GFR) and fractional sodium (Na) excretion in control lambs and lambs treated with a PG synthesis inhibitor, indomethacin. The lambs were 1–2 and 4–6 weeks old and they were studied either during hydropenia (HP) or volume expansion (VE). lndomethacin significantly decreased Na excretion in both groups of hydropenic lambs. lndomethacin also completely blunted the natriuretic response to VE in the older lambs but had no effect on Na excretion in the volume expanded younger lambs. It is concluded that partial lack of PG inhibiting action on tubular Na transport will contribute to the poor natriuretic response to VE in neonatal lambs. Since PG will act locally rather than being blood-borne messengers, the divergent PG action in younger and older lambs might be explained by local differences in maturation of PG metabolism as well as by local differences ir the maturation of PG sensitivity.