Contribution of endothelin to renal vascular tone and autoregulation in the conscious dog

1999 ◽  
Vol 276 (3) ◽  
pp. F417-F424 ◽  
Author(s):  
Heike Berthold ◽  
Klaus Münter ◽  
Armin Just ◽  
Hartmut R. Kirchheim ◽  
Heimo Ehmke
Keyword(s):  
Time Course ◽  
Vascular Tone ◽  
Ace Inhibition ◽  
Renal Hemodynamics ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Renal Autoregulation ◽  
Arterial Blood ◽  
Renal Vascular ◽  
Renal Vascular Tone

Exogenous endothelin-1 (ET-1) is a strong vasoconstrictor in the canine kidney and causes a decrease in renal blood flow (RBF) by stimulating the ETA receptor subtype. The aim of the present study was to investigate the role of endogenously generated ET-1 in renal hemodynamics under physiological conditions. In six conscious foxhounds, the time course of the effects of the selective ETA receptor antagonist LU-135252 (10 mg/kg iv) on mean arterial blood pressure (MAP), heart rate (HR), RBF, and glomerular filtration rate (GFR), as well as its effects on renal autoregulation, were examined. LU-135252 increased RBF by 20% (from 270 ± 21 to 323 ± 41 ml/min, P < 0.05) and HR from 76 ± 5 to 97 ± 8 beats/min ( P< 0.05), but did not alter MAP, GFR, or autoregulation of RBF and GFR. Since a number of interactions between ET-1 and the renin-angiotensin system have been reported previously, experiments were repeated during angiotensin converting enzyme (ACE) inhibition by trandolaprilat (2 mg/kg iv). When ETA receptor blockade was combined with ACE inhibition, which by itself had no effects on renal hemodynamics, marked changes were observed: MAP decreased from 91 ± 4 to 80 ± 5 mmHg ( P < 0.05), HR increased from 85 ± 5 to 102 ± 11 beats/min ( P < 0.05), and RBF increased from 278 ± 23 to 412 ± 45 ml/min ( P< 0.05). Despite a pronounced decrease in renal vascular resistance over the entire pressure range investigated (40–100 mmHg), the capacity of the kidneys to autoregulate RBF was not impaired. The GFR remained completely unaffected at all pressure levels. These results demonstrate that endogenously generated ET-1 contributes significantly to renal vascular tone but does not interfere with the mechanisms of renal autoregulation. If ETAreceptors are blocked, then the vasoconstrictor effects of ET-1 in the kidney are compensated for to a large extent by an augmented influence of ANG II. Thus ET-1 and ANG II appear to constitute a major interrelated vasoconstrictor system in the control of RBF.

Renovascular BKCa channels are not activated in vivo under resting conditions and during agonist stimulation

2007 ◽  
Vol 292 (1) ◽  
pp. R345-R353 ◽  
Author(s):  
Linda Magnusson ◽  
Charlotte Mehlin Sorensen ◽  
Thomas Hartig Braunstein ◽  
Niels-Henrik Holstein-Rathlou ◽  
Max Salomonsson
Keyword(s):  
Vascular Tone ◽  
Ang Ii ◽  
Small Reduction ◽  
Bkca Channels ◽  
Agonist Stimulation ◽  
Electromagnetic Flowmetry ◽  
Renal Vascular ◽  
Renal Vascular Tone

We investigated the role of large-conductance Ca2+-activated K+ (BKCa) channels for the basal renal vascular tone in vivo. Furthermore, the possible buffering by BKCa of the vasoconstriction elicited by angiotensin II (ANG II) or norepinephrine (NE) was investigated. The possible activation of renal vascular BKCa channels by cAMP was investigated by infusing forskolin. Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry or ultrasonic Doppler. Renal preinfusion of tetraethylammonium (TEA; 3.0 μmol/min) caused a small reduction of baseline RBF, but iberiotoxin (IBT; 0.3 nmol/min) did not have any effect. Renal injection of ANG II (1–4 ng) or NE (10–40 ng) produced a transient decrease in RBF. These responses were not affected by preinfusion of TEA or IBT. Renal infusion of the BKCa opener NS-1619 (90.0 nmol/min) did not affect basal RBF or the response to NE, but it attenuated the response to ANG II. Coadministration of NS-1619 with TEA or IBT abolished this effect. Forskolin caused renal vasodilation that was not inhibited by IBT. The presence of BKCa channels in the preglomerular vessels was confirmed by immunohistochemistry. Despite their presence, there is no indication for a major role for BKCa channels in the control of basal renal tone in vivo. Furthermore, BKCa channels do not have a buffering effect on the rat renal vascular responses to ANG II and NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal vascular BKCa channels can be activated under certain conditions.

Angiotensin II inhibition on blood pressure and renal hemodynamics in pregnant rats

1986 ◽  
Vol 250 (2) ◽  
pp. F308-F314 ◽  
Author(s):  
C. Baylis ◽  
R. C. Collins
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics ◽  
Urine Flow ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Acute Surgery ◽  
Arterial Blood ◽  
Renal Vascular

Late-pregnant (18-20 days) and virgin rats were studied under anesthesia or while awake to investigate the effect of acute angiotensin II (ANG II) inhibition (with saralasin or captopril) on mean arterial blood pressure (AP) and renal hemodynamics. ANG II inhibition had no effect on AP in either anesthetized or awake virgin rats. Saralasin produced no effect on renal hemodynamics although with captopril small increases in renal plasma flow rate (RPF) and decreases in renal vascular resistance (RVR) occurred in virgins. In anesthetized pregnant rats, ANG II inhibition evoked marked decreases in AP. In some rats receiving saralasin, AP was only mildly depressed and RVR fell, leading to increases in glomerular filtration rate and RPF. In others, saralasin produced large decreases in AP, and indices of renal function became unmeasurable because of near cessation of urine flow. All late-pregnant anesthetized rats receiving captopril showed increased RPF irrespective of the magnitude of the fall in AP. In awake pregnant rats no effect on AP was seen with ANG II inhibition. Saralasin had no effect on renal hemodynamics although with captopril a small increase in RPF was observed. These data indicate that the stress of acute surgery and anesthesia produces a dependence of AP on ANG II in the pregnant but not the virgin rat. Under normal pregnant (awake) conditions, however, ANG II inhibition has no net effect on AP.

KV7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure

2022 ◽  
Author(s):  
Dieniffer Peixoto-Neves ◽  
Praghalathan Kanthakumar ◽  
Jeremiah M Afolabi ◽  
Hitesh Soni ◽  
Randal K Buddington ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Functional Expression ◽  
Renal Autoregulation ◽  
Neonatal Pigs ◽  
Vascular Smcs ◽  
Neonatal Pig ◽  
Kidney Maturation ◽  
Renal Vascular ◽  
Renal Vascular Tone ◽  
Fetal Pig

KV7, the voltage-gated potassium channels encoded by KCNQ genes, mediate heterogeneous vascular responses in adult rodents. Postnatal changes in the functional expression of KV7 channels have been reported in rodent saphenous arteries, but their physiological function in the neonatal renal vascular bed is unclear. Here, we report that, unlike adult pigs, only KCNQ1 (KV7.1) out of the five members of KCNQ genes was detected in neonatal pig renal microvessels. KCNQ1 is present in fetal pig kidneys as early as day 50 of gestation, and the level of expression remains the same up to postnatal day 21. Activation of the renal vascular smooth muscle cell (SMC) KV7.1 stimulated whole-cell currents, inhibited by HMR1556 (HMR), a selective KV7.1 blocker. HMR did not change the steady-state diameter of isolated renal microvessels. Similarly, intrarenal artery infusion of HMR did not alter the mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) in the pigs. An approximately 20 mmHg reduction in the MAP evoked effective autoregulation of the RBF, which HMR inhibited. We conclude that 1) The expression of KCNQ isoforms in porcine renal microvessels is dependent on kidney maturation, 2) KV7.1 is functionally expressed in neonatal pig renal vascular SMCs, 3) a decrease in arterial pressure up to 20 mmHg induces renal autoregulation in neonatal pigs, and 4) SMC KV7.1 does not control basal renal vascular tone but contributes to neonatal renal autoregulation triggered by a step decrease in arterial pressure.

Role of EP2 and EP3 PGE2receptors in control of murine renal hemodynamics

2001 ◽  
Vol 280 (1) ◽  
pp. H327-H333 ◽  
Author(s):  
Laurent P. Audoly ◽  
Xiaoping Ruan ◽  
Victoria A. Wagner ◽  
Jennifer L. Goulet ◽  
Stephen L. Tilley ◽  
...  
Keyword(s):  
Renal Artery ◽  
Vascular Reactivity ◽  
Renal Hemodynamics ◽  
Receptor Subtypes ◽  
Male Mice ◽  
Unique Role ◽  
Arterial Blood ◽  
Renal Vascular

The kidney plays a central role in long-term regulation of arterial blood pressure and salt and water homeostasis. This is achieved in part by the local actions of paracrine and autacoid mediators such as the arachidonic acid-prostanoid system. The present study tested the role of specific PGE2 E-prostanoid (EP) receptors in the regulation of renal hemodynamics and vascular reactivity to PGE2. Specifically, we determined the extent to which the EP2 and EP3 receptor subtypes mediate the actions of PGE2 on renal vascular tone. Renal blood flow (RBF) was measured by ultrasonic flowmetry, whereas vasoactive agents were injected directly into the renal artery of male mice. Studies were performed on two independent mouse lines lacking either EP2or EP3 (−/−) receptors and the results were compared with wild-type controls (+/+). Our results do not support a unique role of the EP2 receptor in regulating overall renal hemodynamics. Baseline renal hemodynamics in EP2−/− mice [RBF EP2−/−: 5.3 ± 0.8 ml · min−1 · 100 g kidney wt−1; renal vascular resistance (RVR) 19.7 ± 3.6 mmHg · ml−1 · min · g kidney wt] did not differ statistically from control mice (RBF +/+: 4.0 ± 0.5 ml · min−1 · 100 g kidney wt−1; RVR +/+: 25.4 ± 4.9 mmHg · ml−1 · min · 100 g kidney wt−1). This was also the case for the peak RBF increase after local PGE2 (500 ng) injection into the renal artery (EP2−/−: 116 ± 4 vs. +/+: 112 ± 2% baseline RBF). In contrast, we found that the absence of EP3receptors in EP3−/− mice caused a significant increase (43%) in basal RBF (7.9 ± 0.8 ml · min−1 · g kidney wt−1, P < 0.05 vs. +/+) and a significant decrease (41%) in resting RVR (11.6 ± 1.4 mmHg · ml−1 · min · g kidney wt−1, P < 0.05 vs. +/+). Local administration of 500 ng of PGE2 into the renal artery caused more pronounced renal vasodilation in EP3−/− mice (128 ± 2% of basal RBF, P < 0.05 vs. +/+). We conclude that EP3 receptors mediate vasoconstriction in the kidney of male mice and its actions are tonically active in the basal state. Furthermore, EP3receptors are capable of buffering PGE2-mediated renal vasodilation.

Renal hemodynamics and vascular reactivity in canine DOCA-salt hypertension

1988 ◽  
Vol 255 (4) ◽  
pp. R563-R568
Author(s):  
J. L. Goering ◽  
P. C. Raich ◽  
B. G. Zimmerman
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Vascular Tone ◽  
Vascular Reactivity ◽  
Control Period ◽  
Indwelling Catheter ◽  
Alpha Adrenoceptor ◽  
Arterial Blood ◽  
Salt Hypertension ◽  
Renal Vascular

Because of the potential role that the kidney may play in deoxycorticosterone acetate (DOCA)-salt hypertension, changes in renal blood flow, renal vascular reactivity, and renal adrenergic vascular tone were followed in the conscious instrumented dog. DOCA-salt was administered daily after obtaining control measurements. Systemic mean arterial blood pressure (MAP) was monitored with an indwelling catheter, renal blood flow (RBF) was measured electromagnetically using an implanted blood flow probe, and drugs were administered intrarenal arterially through an indwelling renal artery catheter. During the first week of DOCA-salt administration MAP increased from 106 +/- 3 to 118 +/- 2 mmHg and at week 2 to 123 +/- 2 mmHg (P less than 0.01). RBF increased from 275 +/- 32 to 336 +/- 34 during week 1 (P less than 0.05) and to 324 +/- 29 ml/min during week 2. The log ED50 of norepinephrine administered intra-arterially decreased from 1.66 +/- 0.114 to 1.48 +/- 0.091 and 1.41 +/- 0.067 ng/ml (P less than 0.05), and of angiotensin II from 2.58 +/- 0.072 to 2.31 +/- 0.09 (P less than 0.05) and 2.38 +/- 0.05 pg/ml, during weeks 1 and 2, respectively. There was, however, no increase in adrenergic vascular tone as determined by the change in RBF obtained with the intra-arterial infusion of alpha-adrenoceptor antagonists. These experiments indicate that RBF is not compromised in canine DOCA-salt hypertension, and renal adrenergic tone is no greater in the hypertensive than in the normotensive control period.

Effects of blood viscosity on plasma renin activity and renal hemodynamics

1986 ◽  
Vol 250 (1) ◽  
pp. F40-F46 ◽  
Author(s):  
S. Simchon ◽  
R. Y. Chen ◽  
R. D. Carlin ◽  
F. C. Fan ◽  
K. M. Jan ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Blood Viscosity ◽  
Plasma Renin ◽  
Plasma Viscosity ◽  
Renal Hemodynamics ◽  
Renin Activity ◽  
Sodium Pentobarbital ◽  
Coefficient Of Correlation ◽  
Arterial Blood ◽  
Renal Vascular

The effects of alterations in apparent blood viscosity on renal hemodynamics and plasma renin activity (PRA) were studied in dogs anesthetized with sodium pentobarbital. Blood viscosity was altered isovolemically either by changes in hematocrit (Hct) or by an increase in plasma viscosity (dextran administration). Arterial blood pressure and renal blood flow (RBF) remained relatively constant when apparent blood viscosity was elevated by changes in Hct or plasma viscosity. Thus the hyperviscosity of blood was associated with a decrease of renal vascular hindrance, resulting in an essentially unchanged renal flow resistance. The decrease in renal vascular hindrance may result from renal vasodilation. In hyperviscosity induced with dextran, the increase in PRA correlates linearly with the decrease in renal vascular hindrance, with a coefficient of correlation of 0.968 (P less than 0.005). The increase in PRA that resulted when Hct was raised from 25 to 55% also can be correlated linearly with the decrease in renal vascular hindrance, with a coefficient of correlation of 0.953 (P less than 0.005). These results suggest that the decrease in renal vascular hindrance in response to a rise in apparent blood viscosity leads to an increase in PRA.

TP receptors regulate renal hemodynamics during angiotensin II slow pressor response

2004 ◽  
Vol 287 (4) ◽  
pp. F753-F759 ◽  
Author(s):  
Noritaka Kawada ◽  
Kathryn Dennehy ◽  
Glenn Solis ◽  
Paul Modlinger ◽  
Rebecca Hamel ◽  
...  
Keyword(s):  
Pressor Response ◽  
Thiobarbituric Acid ◽  
Ang Ii ◽  
Wild Type ◽  
Thiobarbituric Acid Reactive Substances ◽  
Filtration Fraction ◽  
Arterial Blood ◽  
Tp Receptors ◽  
Prostaglandin H ◽  
Renal Vascular

We investigated the hypothesis that thromboxane A2 (TxA2)-prostaglandin H2 receptors (TP-Rs) mediate the hemodynamic responses and increase in reactive oxygen species (ROS) to ANG II (400 ng·kg−1·min−1 sc for 14 days) using TP-R knockout (TP −/−) and wild-type (+/+) mice. TP −/− had normal basal mean arterial blood pressure (MAP) and glomerular filtration rate but reduced renal blood flow and increased filtration fraction (FF) and renal vascular resistance (RVR) and markers of ROS (thiobarbituric acid-reactive substances and 8-isoprostane PGF2α) and nitric oxide (NOx). Infusion of ANG II into TP +/+ increased ROS and thromboxane B2 (TxB2) and increased RVR and FF. ANG II infusion into TP −/− mice reduced ANG I and increased aldosterone but caused a blunted increase in MAP (TP −/−: +6 ± 2 vs. TP +/+: +15 ± 3 mmHg) and failed to increase FF, ROS, or TxB2 but increased NOx and paradoxically decreased RVR (−2.1 ± 1.7 vs. +2.6 ± 0.8 mmHg·ml−1·min−1·g−1). Blockade of AT1 receptor of TP −/− mice infused with ANG II reduced MAP (−8 mmHg) and aldosterone but did not change the RVR or ROS. In conclusion, during an ANG II slow pressor response, AT1 receptors activate TP-Rs that generate ROS and prostaglandins but inhibit NO. TP-Rs mediate all of the increase in RVR and FF, part of the increase in MAP, but are not implicated in the suppression of ANG I or increase in aldosterone. TP −/− mice have a basal increase in RVR and FF associated with ROS.

Stimulation of renin release by prostaglandin E2 is mediated by EP2 and EP4 receptors in mouse kidneys

2004 ◽  
Vol 287 (3) ◽  
pp. F427-F433 ◽  
Author(s):  
Frank Schweda ◽  
Jürgen Klar ◽  
Shuh Narumiya ◽  
Rolf M. Nüsing ◽  
Armin Kurtz
Keyword(s):  
Vascular Tone ◽  
Threshold Concentration ◽  
Renin Release ◽  
Receptor Subtypes ◽  
Wild Type ◽  
Adrenoceptor Agonist ◽  
Functional Relevance ◽  
Renal Vascular ◽  
Renal Vascular Tone ◽  
Stimulation Of

PGE2 is a potent stimulator of renin release. So far, the contribution of each of the four PGE2 receptor subtypes (EP1–EP4) in the regulation of renin release has not been characterized. Therefore, we investigated the effects PGE2 on renin secretion rates (RSR) from isolated, perfused kidneys of EP1−/−, EP2−/−, EP3−/−, EP4−/−, and wild-type mice. PGE2 concentration dependently stimulated RSR from kidneys of all four knockout strains with a threshold concentration of 1 nM in EP1−/−, EP2−/−, EP3−/−, and wild-type mice, whereas the threshold concentration was shifted to 10 nM in EP4−/− mice. Moreover, the maximum stimulation of RSR by PGE2 at 1 μM was significantly reduced in EP4−/− (12.8-fold of control) and EP2−/− (15.9-fold) compared with wild-type (20.7-fold), EP1−/− (23.8-fold), and EP3−/− (20.1-fold). In contrast, stimulation of RSR by either the loop diuretic bumetanide or the β-adrenoceptor agonist isoproterenol was similar in all strains. PGE2 exerted a dual effect on renal vascular tone, inducing vasodilatation at low concentrations (1 nmol/) and vasoconstriction at higher concentrations (100 nmol/) in kidneys of wild-type mice. In kidneys of EP2−/− as well as EP4−/− mice, vasodilatation at low PGE2 concentrations was prevented, whereas vasoconstriction at higher concentrations was augmented. In contrast, the vasodilatatory component was pronounced in kidneys of EP1 and EP3 knockout mice, whereas in both genotypes the vasoconstriction at higher PGE2 concentrations was markedly blunted. Our data provide evidence that PGE2 stimulates renin release via activation of EP2 and EP4 receptors, whereas EP1 and EP3 receptors appear to be without functional relevance in juxtaglomerular cells. In contrast, all four receptor subtypes are involved in the control of renal vascular tone, EP1 and EP3 receptors increasing, and EP2 as well as EP4 receptors, decreasing it.

Effect of Captopril on Renal Vascular Tone in Patients with Essential Hypertension

1979 ◽  
Vol 57 (s5) ◽  
pp. 421s-423s ◽  
Author(s):  
A. Mimran ◽  
H. R. Brunner ◽  
G. A. Turini ◽  
B. Waeber ◽  
D. Brunner
Keyword(s):  
Essential Hypertension ◽  
Vascular Tone ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Urinary Potassium ◽  
Renal Vascular ◽  
Renal Vascular Tone

1. The effect of acute inhibition of angiotensin-converting enzyme by captopril (50 mg) on renal haemodynamics and function was assessed in nine patients with essential hypertension on unrestricted sodium intake (n = 8) or low sodium diet (n = 1). 2. Captopril induced a rapid and significant decrease in arterial pressure, which was maximal within 60 min. 3. Effective renal plasma flow (ERPF) increased, glomerular filtration rate (GFR) did not change and filtration fraction (FF) decreased after captopril. No change in sodium excretion and a decrease in urinary potassium occurred. 4. In the patient on low sodium diet, captopril induced striking increases in GFR and ERPF (64 and 106% respectively). 5. The logarithm of baseline plasma renin activity was positively correlated with the change in ERPF and negatively correlated with changes in FF and renal resistance. 6. The results indicate that in patients with essential hypertension angiotensin participates actvely in the maintenance of renal vascular tone at the efferent arteriolar level. A possible influence of kinins remains to be defined.

Interactions Between Neural and Hormonal Mediators of Renal Vascular Tone in Anaesthetized Rabbits

2003 ◽  
Vol 88 (2) ◽  
pp. 229-241 ◽  
Author(s):  
Sarah-Jane Guild ◽  
Carolyn J. Barrett ◽  
Roger G. Evans ◽  
Simon C. Malpas
Keyword(s):  
Vascular Tone ◽  
Renal Vascular ◽  
Renal Vascular Tone
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