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.

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.

scholarly journals TRPV4 channels contribute to renal myogenic autoregulation in neonatal pigs

2017 ◽  
Vol 313 (5) ◽  
pp. F1136-F1148 ◽  
Author(s):  
Hitesh Soni ◽  
Dieniffer Peixoto-Neves ◽  
Anberitha T. Matthews ◽  
Adebowale Adebiyi
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cell Swelling ◽  
Transient Receptor Potential Vanilloid ◽  
Channel Blockers ◽  
Renal Autoregulation ◽  
Neonatal Pigs ◽  
Intracellular Ca ◽  
Neonatal Pig ◽  
Transient Receptor

Myogenic response, a phenomenon in which resistance size arteries and arterioles swiftly constrict or dilate in response to an acute elevation or reduction, respectively, in intravascular pressure is a key component of renal autoregulation mechanisms. Although it is well established that the renal system is functionally immature in neonates, mechanisms that regulate neonatal renal blood flow (RBF) remain poorly understood. In this study, we investigated the hypothesis that members of the transient receptor potential vanilloid (TRPV) channels are molecular components of renal myogenic constriction in newborns. We show that unlike TRPV1–3, TRPV4 channels are predominantly expressed in neonatal pig preglomerular vascular smooth muscle cells (SMCs). Intracellular Ca2+ concentration ([Ca2+]i) elevation induced by osmotic cell swelling was attenuated by TRPV4, L-type Ca2+, and stretch-activated Ca2+ channel blockers but not phospholipase A2 inhibitor. Blockade of TRPV4 channels reversed steady-state myogenic tone and inhibited pressure-induced membrane depolarization, [Ca2+]i elevation, and constriction in distal interlobular arteries. A step increase in arterial pressure induced efficient autoregulation of renal cortical perfusion and total RBF in anesthetized and mechanically ventilated neonatal pigs. Moreover, intrarenal arterial infusion of the TRPV4 channel blockers HC 067047 and RN 1734 attenuated renal autoregulation in the pigs. These data suggest that renal myogenic autoregulation is functional in neonates. Our findings also indicate that TRPV4 channels are mechanosensors in neonatal pig preglomerular vascular SMCs and contribute to renal myogenic autoregulation.

Renal autoregulation: perspectives from whole kidney and single nephron studies

1978 ◽  
Vol 234 (5) ◽  
pp. F357-F370 ◽  
Author(s):  
L. G. Navar
Keyword(s):  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Distal Nephron ◽  
Renal Autoregulation ◽  
Single Nephron ◽  
Renal Vascular

The phenomenon of renal autoregulation is often thought to relate only to the manner in which the kidney responds to changes in arterial pressure. This review presents a more comprehensive description of the process based on the intrinsic renal vascular responses to changes in arterial pressure, venous pressure, ureteral pressure, and plasma colloid osmotic pressure. Regulation of glomerular filtration rate (GFR), or some function thereof, is the feature most consistently observed. More specifically, in response to external manipulations that change GFR, autonomous changes in renal vascular resistance tend to return GFR back towards normal. The bulk of the evidence suggests that the requisite renal vascular resistance alterations occur predominately at preglomerular segments. Most of the whole kidney autoregulatory responses can be explained on the basis of the distal tubule-glomerular feedback hypothesis, thought to be mediated by the macula densa-juxtaglomerular complex, which states that increases in distal volume delivery lead to increases in afferent arteriolar resistance while reduced distal delivery leads to afferent arteriolar dilation. Micropuncture data have demonstrated that interruption of distal volume delivery prevents single nephrons from autoregulating GFR and glomerular pressure. Also, single nephron glomerular filtration rate (SNGFR) based on proximal collections is higher than SNGFR measured by distal collections or with an indicator-dilution technique. Studies utilized direct microperfusion of the distal nephron from a late proximal tubule site have demonstrated that SNGFR and glomerular pressure decrease in response to increases in distal nephron perfusion rate. Although experiments in rats have been interpreted as indicating that distal chloride concentration and/or reabsorption most likely mediate the feedback responses, recent studies in dogs have demonstrated that feedback responses can be consistently obtained with nonelectrolyte perfusion solutions. These latter studies suggest that the feedback response may be sensitive to some function of total solute delivery or concentration. At present, there is no clear understanding of the intracellular events that link the compositional alterations occurring within the early distal tubule to the final effector system.

scholarly journals Rehabilitation of patients with chronic pyelonephritis using mineral waters

2020 ◽  
Vol 9 (4) ◽  
pp. 31-36
Author(s):  
Aleksandr I. Nejmark ◽  
Andrej V. Davydov ◽  
Boris A. Nejmark ◽  
Irina V. Kablova
Keyword(s):  
Mineral Water ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Rehabilitation Medicine ◽  
Mineral Waters ◽  
Chronic Pyelonephritis ◽  
Rehabilitation Therapy ◽  
Renal Vascular ◽  
Positive Effect ◽  
Renal Vascular Tone

Relevance. The study of alternative non-drug methods of rehabilitation therapy is an important task in the preventive direction of rehabilitation medicine. An important role in rehabilitation measures to prevent relapse of nephrolithiasis is therapy with the use of balneological therapeutic factors. The purpose of the study is to increase the effectiveness of rehabilitation therapy in patients with chronic pyelonephritis with the use of Serebryaniy klyuch mineral water. Materials and research methods. The basis of the work is the analysis of data from examination and treatment of 48 patients with chronic pyelonephritis in the phase of latent inflammation. All patients included in the study were divided into 2 groups. Patients of the 1st group (n = 23) were prescribed antibacterial, antispasmodic, herbal medicine and drinking fresh water. In addition to standard therapy, patients of the 2nd main group (n = 25) were prescribed 300350 ml of Serebryaniy klyuch mineral water 3040 minutes before meals up to 2 liters per day at a temperature of 3940 C. Results. In patients of the 2nd group in 91.4% of cases, curation of the clinical signs of the disease was noted, pathogens were eliminated in 100% of patients. At the same time, normalization of cytokine homeostasis and humoral immunity was observed, which contributed to a decrease in interstitial edema and normalization of renal vascular tone. Conclusion. The internal intake of Serebryaniy klyuch mineral water in the rehabilitation therapy of patients with chronic pyelonephritis has a positive effect on the elimination of the clinical manifestations of the disease, increases the percentage of sterile urine culture, improves the basal blood flow in the kidneys, the immune status of patients, the cytokine profile of blood serum and there by increases the duration of the full clinical and laboratory remission in this category of patients.

Vasoconstrictor and vasodilator sites within anteroventral third ventricle region

1987 ◽  
Vol 253 (6) ◽  
pp. R827-R831 ◽  
Author(s):  
M. L. Mangiapane ◽  
M. J. Brody
Keyword(s):  
Electrical Stimulation ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Third Ventricle ◽  
Renal Vascular Resistance ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Tungsten Microelectrode ◽  
Renal Vascular ◽  
Stimulation Of

Previous studies have shown that electrical stimulation of the rat anteroventral third ventricle (AV3V) region produces a characteristic pattern of hemodynamic effects, i.e., renal and mesenteric vasoconstriction, and hindquarters vasodilation. In the present study, we localized the vasoconstrictor and vasodilator effects to specific subregions of the AV3V. In urethan-anesthetized rats prepared with arterial catheters and pulsed Doppler flow probes, we assessed the effects of electrical stimulation of four nuclei within AV3V on mean arterial pressure and renal, mesenteric, and hindquarters resistance. These nuclei were the organum vasculosum lamina terminalis (OVLT), ventral nucleus medianus (median preoptic nucleus), anterior (precommissural) nucleus medianus (median preoptic nucleus), and periventricular preoptic nuclei. Stimulation was carried out by use of a tungsten microelectrode. Stimulation of the OVLT consistently provoked stimulus-locked increases in arterial pressure coupled with increases in mesenteric and renal vascular resistance. Ganglionic blockade with chlorisondamine prevented these responses, demonstrating that they were mediated neurogenically. Stimulation of the three remaining nuclei produced decreases in arterial pressure, hindquarters vasodilation, and little change in mesenteric and renal vascular resistance. No changes in heart rate were observed with stimulation of any of the four nuclei. These results suggest that the vasoconstrictor and pressor functions of the AV3V region are localized in or near the OVLT region, whereas the remaining nuclei of the AV3V region mediate vasodilator and depressor responses.

Mechanisms of pressor response produced by stimulation of nucleus ambiguus

1990 ◽  
Vol 259 (5) ◽  
pp. R955-R962
Author(s):  
B. H. Machado ◽  
M. J. Brody
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Pressor Response ◽  
Nucleus Ambiguus ◽  
Ventrolateral Medulla ◽  
Pressor Responses ◽  
Regional Vascular Resistance ◽  
Parasympathetic Control ◽  
Renal Vascular ◽  
Stimulation Of

We showed previously that activation of nucleus ambiguus (NA) induced bradycardia and increased arterial pressure. In this study, we compared responses produced by electrical and chemical (glutamate) stimulation of NA and adjacent rostral ventrolateral medulla (RVLM). Equivalent pressor responses were elicited from both areas. However: 1) The response from RVLM was elicited at a lower frequency. 2) Regional vascular resistance changes were different, i.e., electrical stimulation of NA increased vascular resistance in hindquarters much more than the renal and mesenteric beds. In contrast, electrical and chemical stimulation of RVLM produced a more prominent effect on the renal vascular bed. 3) Bradycardia was elicited from NA at lower current intensity. 4) Glutamate produced bradycardia only when injected into NA. Studies in rats with sinoaortic deafferentation showed that bradycardic response to activation of NA was only partly reflex in origin. We conclude that 1) NA and RVLM control sympathetic outflow to regional vascular beds differentially and 2) the NA region involves parasympathetic control of heart rate and sympathetic control of arterial pressure.

Juxtaglomerular interstitial hypertonicity in Amphiuma: tubular origin-TGF signal

1988 ◽  
Vol 254 (3) ◽  
pp. F445-F449 ◽  
Author(s):  
B. E. Persson ◽  
T. Sakai ◽  
D. J. Marsh
Keyword(s):  
Feedback Inhibition ◽  
Distal Tubule ◽  
Juxtaglomerular Apparatus ◽  
Nacl Transport ◽  
Renal Autoregulation ◽  
Rate Dependent ◽  
Single Nephron ◽  
Tubular Flow ◽  
Renal Vascular ◽  
Vascular Autoregulation

One of the mechanisms mediating renal vascular autoregulation in mammals senses tubular flow rate-dependent changes in luminal NaCl concentrations and signals renal arterioles to change diameter. A similar mechanism operates in the salamander, Amphiuma means. To trace the signal, we measured chloride activity in juxtaglomerular interstitial spaces in Amphiuma during perfusion of the early distal tubule belonging to the same nephron. Interstitial Cl- activity exceeded systemic levels and increased when perfusion rate in the adjacent early distal tubule was increased, reaching values more than five times isotonic. Bumetanide, which inhibits NaCl transport by the early distal tubule, eliminated the hypertonicity. Regions of the interstitial space not a part of the juxtaglomerular apparatus (JGA) were not hypertonic. The Cl- concentration was 80% greater than isotonic in the JGA of nephrons studied under free-flow conditions. Single-nephron blood flow, measured by counting the flux of erythrocytes labeled with a fluorescent molecule, showed typical feedback inhibition with maximum sensitivity to the same rates of tubular perfusion that caused the maximum change in JGA interstitial hypertonicity. Juxtaglomerular interstitial hypertonicity could be an important part of the signal for renal autoregulation.

DISAPPEARANCE OF PROGESTERONE FROM THE SERUM OF NEONATAL PIGS

1980 ◽  
Vol 60 (3) ◽  
pp. 807-809 ◽  
Author(s):  
R.O. PARKER ◽  
T.G. DUNN ◽  
C.C. KALTENBACH
Keyword(s):  
Serum Progesterone ◽  
Blood Samples ◽  
Neonatal Pigs ◽  
Neonatal Pig

Blood samples were drawn from three piglets in each of 10 litters immediately at birth (0 h) and at 6, 12, and 24 h after birth. Progesterone concentrations were measured using radioimmunoassay. At birth, neonatal pig progesterone was 6.3 ± 1.4 ng/mL of serum. By 6 h, serum-progesterone levels dropped (P < 0.05) to 1.6 ± ng/mL. Progesterone levels were 0.9 ± 0.1 ng/mL at 12 h and 0.6 ± 0.7 ng/mL at 24 h; levels at these times were similar to each other but lower (P < 0.05) than 6-h levels.

Acute and chronic actions of bradykinin on renal function and arterial pressure

1985 ◽  
Vol 248 (1) ◽  
pp. F87-F92 ◽  
Author(s):  
J. P. Granger ◽  
J. E. Hall
Keyword(s):  
Arterial Pressure ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Renal Perfusion ◽  
Acute Effects ◽  
Plasma Aldosterone Concentration ◽  
Control Value ◽  
Renal Vascular

The present study was designed to examine the acute and chronic effects of increased levels of circulating bradykinin (BK) on control of renal hemodynamics, electrolyte excretion, and arterial pressure. Intrarenal infusion of BK (50 ng X kg-1 X min-1) for 60 min in five anesthetized dogs with renal perfusion pressure maintained at a constant level of 108 +/- 1 mmHg had no significant effect on glomerular filtration rate (GFR), whereas it increased renal blood flow (RBF) from a control value of 230 +/- 14 to 282 +/- 18, 266 +/- 15, and 253 +/- 17 ml/min after 15, 30, and 60 min of infusion, respectively. Acute intrarenal infusion of BK also increased urine volume (UV) from 0.255 +/- 0.044 to 0.523 +/- 0.103 ml/min and urinary sodium excretion (UNaV) from 5.72 +/- 1.5 to 13.7 +/- 3.4 mueq/min. To determine whether the potent acute effects of BK on RBF, UV, and UNaV lead to a chronic reduction in arterial pressure, BK (50 ng X kg-1 X min-1) was infused intrarenally for 7 days in conscious dogs. Intrarenal infusion of BK for 7 days had no significant effect on GFR, UNaV, UV, or arterial pressure. However, BK elevated renal plasma flow and decreased renal vascular resistance throughout the 7 days of infusion. Chronic intrarenal BK infusion caused no significant changes in plasma renin activity or plasma aldosterone concentration. Results from these studies indicate that although increased levels of bradykinin in the renal circulation can have potent acute effects on RBF, UV, and UNaV, these effects on UV and UNaV are not sustained and therefore do not result in long-term changes in arterial pressure.

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