Plasma dopamine in regulation of canine renal blood flow

1988 ◽  
Vol 255 (3) ◽  
pp. R379-R387 ◽  
Author(s):  
D. R. Kapusta ◽  
N. W. Robie

Studies were performed in pentobarbital-anesthetized dogs to determine whether circulating plasma dopamine (DA) is involved in renal blood flow (RBF) regulation. During graded reductions in renal perfusion pressure (RPP), total renal venous (RV) DA content significantly increased at RPPs below the autoregulatory range. The RBF response to decrements in RPP was also examined during control, infusion of DA (1.2 micrograms.kg(-1).min(-1)ia), and after DA receptor blockade by SCH 23390 (30 micrograms/kg iv). During DA infusion, autoregulation was still evident over the same RPPs, although at higher flow rates. At pressures below the autoregulatory range, RBF decreased linearly and the autoregulatory curve merged with control at 50 mmHg. After SCH 23390, autoregulation ceased at a higher RPP than during control, and RBF was significantly less than control rates at pressures of 80 mmHg and below. To elucidate reasons for this latter response, reductions in RPP were repeated before and after administration of both prazosin (0.1 mg/kg iv) and SCH 23390. The results indicated that RBF rates were not different from control at any RPP. Further, prazosin alone did not alter renal autoregulation but significantly increased RBF at RPP below the autoregulatory range. Thus these results indicate that dopamine does not participate in RBF control at pressures above the inflection point for the lowest limit of RBF autoregulation but may be released at lower RPP to act as a vasodilator agent to oppose alpha-adrenoceptor-mediated reductions in RBF. Moreover, tonic DA receptor activation may influence the setting of the lower limit of canine RBF autoregulation.

1985 ◽  
Vol 248 (3) ◽  
pp. F366-F373 ◽  
Author(s):  
A. J. Premen ◽  
J. E. Hall ◽  
H. L. Mizelle ◽  
J. E. Cornell

Adenosine has been postulated to link control of glomerular filtration rate (GFR) and renal blood flow (RBF) with changes in renal metabolism. In the present study, we examined the role of adenosine in renal autoregulation by comparing the responses of normal anesthetized dogs to step decreases in renal artery pressure (RAP) to the response obtained after receptor blockade of adenosine with aminophylline or by flooding the kidney with exogenous adenosine. In six dogs at normal RAP, intrarenal infusion of aminophylline (10 mumol/min) did not alter renal hemodynamics. GFR and RBF were well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after aminophylline. At RAP equal to 75 mmHg, GFR and RBF decreased by 27 +/- 10 and 20 +/- 8%, respectively, before aminophylline and by 25 +/- 7 and 13 +/- 6% after aminophylline. In a different group of six dogs, intrarenal infusion of adenosine (6 mumol/min) significantly increased RBF (32 +/- 9%) and decreased GFR (38 +/- 10%) at normal RAP. However, GFR and RBF were both well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after adenosine. At RAP equal to 75 mmHg, GFR and RBF decreased by 10 +/- 5 and 7 +/- 3%, respectively, before adenosine and by 12 +/- 6 and 17 +/- 5% after adenosine. Neither aminophylline nor adenosine attenuated the elevations in plasma renin activity associated with reductions in RAP. These data fail to provide evidence that adenosine is an important factor in autoregulation of GFR and RBF during acute reductions in RAP within the autoregulatory range.


1985 ◽  
Vol 249 (2) ◽  
pp. F236-F240 ◽  
Author(s):  
E. D. Frederickson ◽  
T. Bradley ◽  
L. I. Goldberg

Dopamine (DA) acts on two receptor subtypes, DA1 and DA2. The purpose of this study was to determine which subtype is involved in the increments in renal blood flow (RBF) and electrolyte excretion produced by DA. Mongrel dogs were anesthetized with pentobarbital sodium. Phenoxybenzamine (10 mg X kg-1 ia) and propranolol (5 mg X kg-1 iv) were administered to exclude effects mediated by alpha- and beta-adrenoceptors. DA was infused into the renal artery before and after administration of either the selective DA1 antagonist SCH 23390 or the selective DA2 antagonist domperidone. With DA alone, RBF increased by 52 +/- 7%, Na+ excretion increased by 35 +/- 8%, and K+ excretion increased by 35 +/- 5%. Infusion of SCH 23390 (0.5 micrograms X kg-1 X min-1) completely blocked DA-induced increase in RBF and electrolyte excretion. Intravenous infusion of domperidone (1 microgram X kg-1 X min-1) did not attenuate the responses to DA. Neither SCH 23390 nor domperidone affected base-line RBF or electrolyte excretion, suggesting that in these experiments endogenous DA was not active. In conclusion, these data indicate that the effects of DA to increase RBF and electrolyte excretion are the result of action on DA1 receptors.


2010 ◽  
Vol 298 (6) ◽  
pp. F1360-F1368 ◽  
Author(s):  
David A. Osmond ◽  
Edward W. Inscho

In vitro experiments demonstrate that P2X1 receptor activation is important for normal afferent arteriolar autoregulatory behavior, but direct in vivo evidence for this relationship occurring in the whole kidney is unavailable. Experiments were performed to test the hypothesis that P2X1 receptors are important for autoregulation of whole kidney blood flow. Renal blood flow (RBF) was measured in anesthetized male Sprague-Dawley rats before and during P2 receptor blockade with PPADS, P2X1 receptor blockade with IP5I, or A1 receptor blockade with DPCPX. Both P2X1 and A1 receptor stimulation with α,β-methylene ATP and CPA, respectively, caused dose-dependent decreases in RBF. Administration of either PPADS or IP5I significantly blocked P2X1 receptor stimulation. Likewise, administration of DPCPX significantly blocked A1 receptor activation to CPA. Autoregulatory behavior was assessed by measuring RBF responses to reductions in renal perfusion pressure. In vehicle-infused rats, as pressure was decreased from 120 to 100 mmHg, there was no decrease in RBF. However, in either PPADS- or IP5I-infused rats, each decrease in pressure resulted in a significant decrease in RBF, demonstrating loss of autoregulatory ability. In DPCPX-infused rats, reductions in pressure did not cause significant reductions in RBF over the pressure range of 100–120 mmHg, but the autoregulatory curve tended to be steeper than vehicle-infused rats over the range of 80–100 mmHg, suggesting that A1 receptors may influence RBF at lower pressures. These findings are consistent with in vitro data from afferent arterioles and support the hypothesis that P2X1 receptor activation is important for whole kidney autoregulation in vivo.


2019 ◽  
Vol 51 (3) ◽  
pp. 90-96 ◽  
Author(s):  
J. D. Pressly ◽  
H. Soni ◽  
S. Jiang ◽  
J. Wei ◽  
R. Liu ◽  
...  

Acute kidney injury (AKI) is an increasing clinical problem that is associated with chronic kidney disease progression. Cannabinoid receptor 2 (CB2) activation has been shown to mitigate some of the deleterious tubular effects due to AKI, but its role on the renal vasculature has not been fully described. In this study, we investigated the effects of our novel CB2 receptor agonist, SMM-295, on renal vasculature by assessing cortical perfusion with laser Doppler flowmetry and changes in luminal diameter with isolated afferent arterioles. In this study, intravenously infused SMM-295 (6 mg/kg) significantly increased cortical renal perfusion (13.8 ± 0.6%; P < 0.0001; n = 7) compared with vehicle (0.1 ± 1.5%; n = 10) normalized to baseline values in anesthetized C57BL/6J mice. This effect was not dependent upon activation of the CB1 receptor (met-anandamide; 6 mg/kg iv) and was predominantly abolished in Cnr2 knockout mice with SMM-295 (6 mg/kg iv). Ablation of the renal afferent nerves with capsaicin blocked the SMM-295-dependent increase in renal cortical perfusion, and the increased renal blood flow was not dependent upon products synthesized by cyclooxygenase or nitric oxide synthase. The increased renal perfusion by CB2 receptor activation is also attributed to a direct vascular effect, since SMM-295 (5 μM) engendered a significant 37 ± 7% increase ( P < 0.0001; n = 4) in luminal diameters of norepinephrine-preconstricted afferent arterioles. These data provide new insight into the potential benefit of SMM-295 by activating vascular and nonvascular CB2 receptors to promote renal vasodilation, and provide a new therapeutic target to treat renal injuries that impact renal blood flow dynamics.


1987 ◽  
Vol 252 (1) ◽  
pp. F65-F73 ◽  
Author(s):  
L. L. Woods ◽  
H. L. Mizelle ◽  
J. E. Hall

The purpose of this study was to test the hypothesis that hyperglycemia, comparable with that found in uncontrolled diabetes mellitus, increases renal blood flow (RBF) and glomerular filtration rate (GFR) through a tubuloglomerular feedback (TGF) mechanism. We infused glucose intrarenally (0.1-0.3 g/min) into anesthetized dogs with normal kidneys (NK), with nonfiltering kidneys (NFK) in which changes in TGF were blocked, and with normal kidneys in which renal perfusion pressure (RAP) was lowered to the limits of renal autoregulation (LPK). Calculated intrarenal plasma glucose levels rose to 250-400 mg/dl. In NK (n = 6) RBF and GFR increased by 18 +/- 3 and 19 +/- 5%, respectively, and renal vascular resistance fell by 17 +/- 2% after 90 min. The renal hemodynamic responses to glucose were abolished in NFK (n = 8); RBF averaged 96 +/- 4% of control after 60 min of hyperglycemia. RBF and GFR did not change during hyperglycemia in LPK (n = 5), averaging 96 +/- 1 and 100 +/- 8% of control, respectively, after 60 min. Autoregulation of RBF and GFR during reductions in RAP was impaired during hyperglycemia in NK; RBF and GFR were effectively autoregulated between RAP of 126 and 70-85 mmHg during the control period, whereas during glucose infusion RBF and GFR fell by 31 +/- 9 and 47 +/- 10%, respectively, when RAP was reduced in steps to 70 mmHg. These data suggest that hyperglycemia impairs renal autoregulation and may increase renal blood flow and GFR through a tubuloglomerular feedback mechanism.


2019 ◽  
Vol 31 (2) ◽  
pp. 324-336 ◽  
Author(s):  
Anil K. Bidani ◽  
Aaron J. Polichnowski ◽  
Hector Licea-Vargas ◽  
Jianrui Long ◽  
Stephanie Kliethermes ◽  
...  

BackgroundRenal autoregulation maintains stable renal function despite BP fluctuations and protects glomerular capillaries from hypertensive injury. However, real-time dynamics of renal autoregulation in conscious animals have not been characterized.MethodsTo develop novel analytic methods for assessing renal autoregulation, we recorded concurrent BP and renal blood flow in conscious rats, comparing animals with renal autoregulation that was intact versus impaired (from 3/4 nephrectomy), before and after additional impairment (from the calcium channel blocker amlodipine). We calculated autoregulatory indices for adjacent short segments of increasing length (0.5, 1, 2.5, 5, 10, and 20 seconds) that exhibited a mean BP difference of at least 5 mm Hg.ResultsAutoregulatory restoration of renal blood flow to baseline after BP changes in conscious rats occurs rapidly, in 5–10 seconds. The response is significantly slower in states of impaired renal autoregulation, enhancing glomerular pressure exposure. However, in rats with severe renal autoregulation impairment (3/4 nephrectomy plus amlodipine), renal blood flow in conscious animals (but not anesthetized animals) was still restored to baseline, but took longer (15–20 seconds). Consequently, the ability to maintain overall renal blood flow stability is not compromised in conscious rats with impaired renal autoregulation.ConclusionsThese novel findings show the feasibility of renal autoregulation assessment in conscious animals with spontaneous BP fluctuations and indicate that transient increases in glomerular pressure may play a greater role in the pathogenesis of hypertensive glomerulosclerosis than previously thought. These data also show that unidentified mechanosensitive mechanisms independent of known renal autoregulation mechanisms and voltage-gated calcium channels can maintain overall renal blood flow and GFR stability despite severely impaired renal autoregulation.


2013 ◽  
Vol 304 (11) ◽  
pp. R929-R939 ◽  
Author(s):  
Christopher G. Scully ◽  
Nicholas Mitrou ◽  
Branko Braam ◽  
William A. Cupples ◽  
Ki H. Chon

Laser speckle perfusion imaging (LSPI) has become an increasingly popular technique for monitoring vascular perfusion over a tissue surface. However, few studies have utilized the full range of spatial and temporal information generated by LSPI to monitor spatial properties of physiologically relevant dynamics. In this study, we extend the use of LSPI to analyze renal perfusion dynamics over a spatial surface of ∼5 × 7 mm of renal cortex. We identify frequencies related to five physiological systems that induce temporal changes in renal vascular perfusion (cardiac flow pulse, respiratory-induced oscillations, baroreflex components, the myogenic response, and tubuloglomerular feedback) across the imaged surface and compare the results with those obtained from renal blood flow measurements. We find that dynamics supplied from global sources (cardiac, respiration, and baroreflex) present with the same frequency at all locations across the imaged surface, but the local renal autoregulation dynamics can be heterogeneous in their distribution across the surface. Moreover, transfer function analysis with forced blood pressure as the input yields the same information with laser speckle imaging or renal blood flow as the output during control, intrarenal infusion of Nω-nitro-l-arginine methyl ester to enhance renal autoregulation, and intrarenal infusion of the rho-kinase inhibitor Y-27632 to inhibit vasomotion. We conclude that LSPI measurements can be used to analyze local as well as global renal perfusion dynamics and to study the properties of physiological systems across the renal cortex.


1994 ◽  
Vol 267 (1) ◽  
pp. R253-R259 ◽  
Author(s):  
D. M. Strick ◽  
M. J. Fiksen-Olsen ◽  
J. C. Lockhart ◽  
R. J. Roman ◽  
J. C. Romero

We studied the responses of total renal blood flow (RBF) and renal medullary blood flow (RMBF) to changes in renal perfusion pressure (RPP) within and below the range of renal autoregulation in the anesthetized dog (n = 7). To measure RMBF, we developed a technique in which the medulla is exposed by excising a section of infarcted cortex and a multiple optical fiber flow probe, connected to a laser-Doppler flowmeter, is placed on the medulla. At the baseline RPP of 120 +/- 1 mmHg, RBF was 2.58 +/- 0.33 ml.min-1.g perfused kidney wt-1, and RMBF was 222 +/- 45 perfusion units. RPP was then decreased in consecutive 20-mmHg steps to 39 +/- 1 mmHg. At 80 +/- 1 mmHg, RBF remained at 89 +/- 4% of the baseline value; however, RMBF had decreased significantly (P < 0.05) to 73 +/- 4% of its baseline value. The efficiency of autoregulation of RBF and of RMBF within the RPP range of 120 to 80 mmHg was determined by calculating an autoregulatory index (AI) for each parameter using the formula AI = (%delta blood flow)/(%delta RPP). An AI of 0 indicates perfect autoregulation, and an index of 1 indicates a system with a fixed resistance. The AI for RBF averaged 0.33 +/- 0.12 over this pressure range and showed a significantly greater (P < 0.05) autoregulatory ability than did the RMBF (0.82 +/- 0.13). Decreasing perfusion pressure < 80 mmHg produced significant decreases in both RBF and RMBF.(ABSTRACT TRUNCATED AT 250 WORDS)


1975 ◽  
Vol 229 (4) ◽  
pp. 983-988 ◽  
Author(s):  
PA Jose ◽  
LM Slotkoff ◽  
S Montgomery ◽  
PL Calcagno ◽  
G Eisner

The ability of the immature kidney to autoregulate blood flow was investigated. Renal blood flow was measured by electromagnetic flowmeter. In six puppies, selective blockade of the intrarenal effects of angiotensin II (AII) by [1-sarcosine, 8-alanine]angiotensin II (anti-AII) administered into the renal artery did not change renal blood flow. During selective renal AII blockade, intravenous AII raised perfusion pressure from 76 +/- 2 to 100 +/- 6 mmHg. Renal blood flow increased from 1.59 +/- 0.29 to 1.98 +/- 0.59 ml/g kidney per min, but returned to control levels within 40 s in spite of persistent arterial pressure elevation. In another group of seven puppies, renal blood flow remained constant despite reduction of renal perfusion pressure by aortic constriction to 60 mmHg. In two of these seven puppies intrarenal anti-AII did not abolish autoregulation. Autoregulation of renal blood flow occurs in the puppy and is not influenced by inhibition of angiotensin. The renin-angiotensin system does not appear to be involved in the normal regulation of renal blood flow in the puppy.


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