Magnitude of TGF-initiated nephron-nephron interactions is increased in SHR

1995 ◽  
Vol 269 (2) ◽  
pp. F198-F204 ◽  
Author(s):  
Y. M. Chen ◽  
K. P. Yip ◽  
D. J. Marsh ◽  
N. H. Holstein-Rathlou
Keyword(s):  
Interaction Strength ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Vascular Connection ◽  
Spontaneously Hypertensive ◽  
Sd Rats ◽  
Flow Pressure ◽  
Stop Flow ◽  
Account Interaction

We compared the tubuloglomerular feedback (TGF)-initiated nephron-nephron interaction in spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley (SD) rats. Interaction strength was assessed by measuring stop-flow pressure (delta SFP) responses in pairs of nephrons, where only one nephron of the pair was microperfused. The vascular connection was determined from casts of the nephrons and vessels; length of arteriolar separation between the two glomeruli was measured on the casts. When microperfusion rate was increased from 5 to 50 nl/min, delta SFP in perfused nephrons was 10.6 +/- 0.6 and 10.2 +/- 0.7 mmHg [not significant (NS)] in SD and SHR, respectively. In the matched unperfused nephrons from the same cortical radial artery, delta SFP was 1.3 +/- 0.2 and 2.9 +/- 0.7 mmHg (P < 0.05) in SD and SHR. When the perfused and unperfused nephron originated from different cortical radial arteries, delta SFP in the unperfused nephrons was -0.1 +/- 0.2 and 0.0 +/- 0.3 mmHg (NS) in SD and SHR, respectively. In both strains, interaction strength varied inversely with glomerular separation. When the dependence on distance was taken into account, interaction strength was about threefold greater in SHR than in SD. We conclude that the nephron-nephron interaction is significantly greater in SHR. The dependence of interaction strength on distance separating the glomeruli suggests that the interaction is propagated along the preglomerular vasculature.

Impaired effect of nitric oxide synthesis inhibition on tubuloglomerular feedback in hypertensive rats

1996 ◽  
Vol 271 (2) ◽  
pp. F246-F252 ◽  
Author(s):  
C. Thorup ◽  
A. E. Persson
Keyword(s):  
Nitric Oxide ◽  
Flow Rate ◽  
Turning Point ◽  
Tubuloglomerular Feedback ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Wistar Kyoto ◽  
Stop Flow

Experiments were conducted to compare the effects of intratubular inhibition [N omega-nitro-L-arginine (L-NNA)] of nitric oxide (NO) on the tubuloglomerular feedback (TGF) mechanism between anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and between the Milan hypertensive (MHS) and the Milan normotensive (MNS) strains of rats. Changes in proximal tubular stop-flow pressure (Psf) in response to various loop of Henle perfusion rates and measurements of early proximal flow rate (EPFR) were used to characterize TGF. Maximal drop in Psf (delta Psf) were used to indicate TGF reactivity and the flow rate eliciting half-maximal delta Psf (turning point; TP) to indicate TGF sensitivity. Under control conditions, TGF sensitivity was significantly higher in SHR than in WKY, but, after L-NNA infusion, TP was decreased in WKY and not in SHR. L-NNA infusion increased delta Psf by 95% in WKY but to a lesser extent (by 26%) in SHR. In the same way, L-NNA decreased TP in MNS but not in MHS. The increase in delta Psf was 99% in MNS but only 32% in MHS. The EPFR reduction after TGF activation was significantly increased in WKY and MNS but relatively unchanged in SHR and MHS. The results show that the effect of intratubular NO synthase inhibition on TGF is impaired in both strains of hypertensive rats.

scholarly journals Testosterone enhances tubuloglomerular feedback by increasing superoxide production in the macula densa

2013 ◽  
Vol 304 (9) ◽  
pp. R726-R733 ◽  
Author(s):  
Yiling Fu ◽  
Yan Lu ◽  
Eddie Y. Liu ◽  
Xiaolong Zhu ◽  
Gouri J. Mahajan ◽  
...  
Keyword(s):  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Mediated Effects ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Laser Capture ◽  
Stop Flow ◽  
Dependent Pathway

Males have higher prevalence of hypertension and renal injury than females, which may be attributed in part to androgen-mediated effects on renal hemodynamics. Tubuloglomerular feedback (TGF) is an important mechanism in control of renal microcirculation. The present study examines the role of testosterone in the regulation of TGF responses. TGF was measured by micropuncture (change of stop-flow pressure, ΔPsf) in castrated Sprague-Dawley rats. The addition of testosterone (10−7 mol/l) into the lumen increased the ΔPsf from 10.1 ± 1.2 to 12.2 ± 1.2 mmHg. To determine whether androgen receptors (AR) are involved, mRNA of AR was measured in the macula dense cells isolated by laser capture microdissection from kidneys, and a macula densa-like cell line (MMDD1). AR mRNA was expressed in the macula densa of rats and in MMDD1 cells. We next examined the effects of the AR blocker, flutamide (10−5 mol/l) on the TGF response. The addition of flutamide blocked the effects of testosterone on TGF. The addition of Tempol (10−4 mol/l) or polyethylene glycol-superoxide dismutase (100 U/ml) to scavenge superoxide blocked the effect of testosterone to augment TGF. We then applied apocynin to inhibit NAD(P)H oxidase and oxypurinol to inhibit xanthine oxidase and found the testosterone-induced augmentation of TGF was blocked. In additional experiments in MMDD1 cells, we found that testosterone increased O2− generation. Apocynin or oxypurinol blocked the testosterone-induced increases of O2−, while blockade of COX-2 with NS-398 had no effect. These findings suggest that testosterone enhances TGF response by stimulating O2− production in macula densa via an AR-dependent pathway.

Overflow of endogenous norepinephrine from PVH nucleus of DOCA-salt hypertensive rats

1995 ◽  
Vol 268 (4) ◽  
pp. H1549-H1554 ◽  
Author(s):  
J. M. Qualy ◽  
T. C. Westfall
Keyword(s):  
Sodium Nitroprusside ◽  
Genetic Model ◽  
Spontaneously Hypertensive Rat ◽  
Tap Water ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Sd Rats ◽  
Salt Hypertension ◽  
Wistar Kyoto

Previous studies from this laboratory demonstrated that there was enhanced basal and evoked (K+ depolarization) overflow of endogenous norepinephrine (NE) into the perfusate of a push-pull cannula placed in the paraventricular nucleus of the hypothalamus (PVH) of conscious freely moving spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKY) or Sprague-Dawley (SD) rats. The present study was carried out to determine whether results obtained with SHR were specific to this genetic model of hypertension by examining NE release in deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt hypertension was produced in 8-wk-old uninephrectomized SD rats by administering a 50-mg DOCA Silastic pellet subcutaneously 7 days postnephrectomy and providing 0.9% NaCl + 0.2% KCl drinking solution at libitum for 3 wk. Sham-implanted animals received normal tap water. Blood pressure was similar to that of 8- to 10-wk-old SHR. Basal release of NE as well as release after K+ added to the push-pull cannula or sodium nitroprusside or phenylphrine administered intravenously was determined. It was observed that there was no difference in basal overflow or after K+ administration in DOCA-salt hypertensive rats compared with sham animals. Similarly, the increase in NE overflow due to sodium nitroprusside or the decrease due to phenylphrine was similar between DOCA-salt rats or sham controls. This was in sharp contrast to what was observed in SHR: basal or K(+)-evoked release was significantly greater in SHR than WKY, SD, DOCA-salt, or DOCA-sham controls. It is concluded that central noradrenergic activity involving the PVH is not altered in DOCA-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Adenosine A2 receptors modulate tubuloglomerular feedback

2010 ◽  
Vol 299 (2) ◽  
pp. F412-F417 ◽  
Author(s):  
Mattias Carlström ◽  
Christopher S. Wilcox ◽  
William J. Welch
Keyword(s):  
Receptor Antagonist ◽  
Low Dose ◽  
Tubuloglomerular Feedback ◽  
High Dose ◽  
Sprague Dawley ◽  
Simultaneous Application ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Stop Flow ◽  
A2 Receptors

Adenosine can mediate the tubuloglomerular (TGF) response via activation of A1 receptors on the afferent arteriole, but both adenosine A1 and A2 receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A2 receptors offset the effect of A1 receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (ΔPSF) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min of intratubular perfusion (10 nl/min) with ATF alone, or with ATF plus the A2A receptor antagonist (ZM-241385; 10−7 or 10−5 mol/l), A1 receptor antagonist (PSB-36; 10−8 mol/l), or with a combination of A1 (PSB-36; 10−8 mol/l) and A2A (ZM-241385; 10−7 mol/l) antagonists. The maximal TGF response (ΔPSF) with ATF alone was 11.7 ± 1.0 mmHg. Specific A2 inhibition (low dose) enhanced the maximal TGF response (15.7 ± 0.8 mmHg; P < 0.01), whereas a high dose (unspecific inhibition) attenuated the response (5.0 ± 0.4 mmHg; P < 0.001). A1 inhibition alone led to a paradoxical TGF response, with an increase in PSF of 3.1 ± 0.5 mmHg ( P < 0.05). Simultaneous application of A1 and A2 antagonists abolished the TGF response (ΔPSF: 0.4 ± 0.3 mmHg). In conclusion, adenosine A2 receptors modulate the TGF response by counteracting the effects of adenosine A1 receptors.

Internephron coupling by conducted vasomotor responses in normotensive and spontaneously hypertensive rats

1997 ◽  
Vol 272 (3) ◽  
pp. F372-F379 ◽  
Author(s):  
A. J. Wagner ◽  
N. H. Holstein-Rathlou ◽  
D. J. Marsh
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Afferent Arteriole ◽  
Stimulation Site ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Vascular Events ◽  
Spontaneously Hypertensive ◽  
Vasomotor Responses ◽  
Sd Rats ◽  
Afferent Arterioles

We compared conducted vasomotor responses in juxtamedullary microcirculation in normotensive Sprague-Dawley (SD) and spontaneously hypertensive rats (SHR). The goals of the study were as follows: 1) decide whether internephron coupling is facilitated by conducted vasomotor responses; 2) determine whether the magnitude of induced vasoconstriction decreases with increasing distance from the stimulation site; and 3) determine whether the response is stronger in SHR than in SD rats. Microapplication of KCl to the distal afferent arteriole caused local vasoconstriction that was rapidly conducted (speed > 3.0 mm/s) into the cortical radial artery and neighboring afferent arterioles in SD and SHR. The strength of the response was significantly greater (approximately 40%, P < 0.025) in SHR than SD, and the magnitude decreased monotonically with increasing distance from the stimulation site in both strains. Mechanical length constants were similar in SD and SHR (approximately 325 microm), indicating that the signal responsible for the effect decays at the same rate in both strains. We conclude that internephron coupling strength is significantly greater in SHR and that internephron coupling is due to vascular events conducted along the preglomerular vasculature.

Enhanced tubuloglomerular feedback activity in rats developing spontaneous hypertension

1984 ◽  
Vol 247 (4) ◽  
pp. F672-F679 ◽  
Author(s):  
J. R. Dilley ◽  
W. J. Arendshorst
Keyword(s):  
Arterial Pressure ◽  
Strain Differences ◽  
Tubuloglomerular Feedback ◽  
Adult Rats ◽  
Spontaneously Hypertensive ◽  
Single Nephron ◽  
Flow Through ◽  
Flow Pressure ◽  
Wistar Kyoto ◽  
Stop Flow

Tubular microperfusion was used to evaluate tubuloglomerular feedback (TGF)-mediated changes in single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) in euvolemic 6- and 11- to 14-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Young SHR compared with WKY had an elevated mean arterial pressure (107 vs. 90 mmHg, P less than 0.001) and a lower proximally measured SNGFR (14 vs. 17 nl/min, P less than 0.001) with no loop perfusion. Perfusion at 32 nl/min produced a greater decrease in SNGFR of SHR (6 vs. 2 nl/min, P less than 0.001). Although basal SFPs were identical (39 mmHg), loop perfusion elicited a greater maximal decline in SFP (-10 vs. -4 mmHg, P less than 0.001) and reactivity of SFP (-1.2 vs. -0.5 mmHg X min X nl-1, P less than 0.001) in young SHR; a lower rate produced a half-maximal decrease in SFP (7 vs. 10 nl/min, P less than 0.02). In adult rats, SNGFRs with no flow through Henle's loop were the same (27 and 28 nl/min) and perfusion at 32 nl/min produced similar decrements in SNGFR (-13 vs. -11 nl/min). The maximal change in SFP was greater in adult SHR (-12 vs. -10 mmHg, P less than 0.02), but there were no strain differences in maximal SFP reactivity (-1.8 vs. -1.3 mmHg X min X nl-1) and the rate eliciting half-maximal SFP changes (12 vs. 12 nl/min). Reduction of arterial pressure to the normotensive range did not alter responses in either age group of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences In Utero in Activities of Catecholamine Biosynthetic Enzymes in Adrenals of Spontaneously Hypertensive Rats

1981 ◽  
Vol 61 (s7) ◽  
pp. 227s-230s ◽  
Author(s):  
G. Teitelman ◽  
R. A. Ross ◽  
T. H. Joh ◽  
D. J. Reis
Keyword(s):  
Adrenal Medulla ◽  
Spontaneously Hypertensive Rats ◽  
Sympathetic Ganglia ◽  
Biosynthetic Enzymes ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Catecholamine Biosynthesis ◽  
Sd Rats ◽  
Wistar Kyoto

1. We sought to determine if catecholamine biosynthetic enzymes of spontaneously hypertensive rats (SHR) differed from those of normotensive Wistar—Kyoto (WKY) and Sprague—Dawley (SD) control rats before birth. 2. By immunocytochemical and biochemical methods we compared strains for the time of appearance and maturation of the enzymes tyrosine hydroylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) in sympathetic ganglia and adrenals. 3. The time of appearance of enzymes was identical in all three strains: TH and DBH first appeared in sympathetic ganglia on embryonic day 11 (E11) and in adrenal medulla on E16. PNMT, restricted to adrenal medulla, appeared later on E18. 4. The activity of adrenal TH prenatally on E18 and E21 and at day of birth (P1) in SHR was approximately two fold that in WKY or SD rats. In contrast PNMT was lower in SHR but only on E18. 5. Thus, although the timing of the first expression of adrenergic phenotypes is similar in SHR and normotensive controls, the differences in TH activity in adrenals suggest an enhanced biosynthetic capacity for catecholamines in this strain before birth. 6. We conclude that SHR differ from normotensive rats from the first expression of some of the genes controlling catecholamine biosynthesis.

Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in ovariectomized spontaneously hypertensive rats

2010 ◽  
Vol 299 (2) ◽  
pp. H265-H274 ◽  
Author(s):  
Marek Jankowski ◽  
Donghao Wang ◽  
Bogdan Danalache ◽  
Marius Gangal ◽  
Jolanta Gutkowska
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Sd Rats ◽  
Ovx Rats ◽  
Endothelial Nitric Oxide

An increasing amount of evidence demonstrates the beneficial role of oxytocin (OT) in the cardiovascular system. Similar actions are attributed to genistein, an isoflavonic phytoestrogen. The treatment with genistein activates the OT system in the aorta of ovariectomized (OVX) Sprague-Dawley (SD) rats. The objective of this study was to determine the effects of low doses of genistein on the OT-induced effects in rat hypertension. The hypothesis tested was that treatment of OVX spontaneously hypertensive rats (SHRs) with genistein improves heart structure and heart work through a mechanism involving the specific OT receptor (OTR). OVX SHRs or SD rats were treated with genistein (in μg/g body wt sc, 10 days) in the presence or absence of an OT antagonist (OTA) [d(CH2)5, Tyr(Me)2, Orn8]-vasotocin or a nonspecific estrogen receptor antagonist (ICI-182780). Vehicle-treated OVX rats served as controls. RT-PCR and Western blot analysis demonstrated that left ventricular (LV) OTR, downregulated by ovariectomy, increased in response to genistein. In SHRs or SD rats, this effect was blocked by OTA or ICI-182780 administration. The OTR was mainly localized in microvessels expressing the CD31 marker and colocalized with endothelial nitric oxide synthase. In SHRs, the genistein-stimulated OTR increases were associated with improved fractional shortening, decreased blood pressure (12 mmHg), decreased heart weight-to-body weight ratio, decreased fibrosis, and lowered brain natriuretic peptide in the LV. The prominent finding of the study is the detrimental effect of OTA treatment on the LV of SHRs. OTA treatment of OVX SHRs resulted in a dramatic worsening of ejection fractions and an augmented fibrosis. In conclusion, these results demonstrate that cardiac OTRs are involved in the regulation of cardiac function of OVX SHRs. The decreases of OTRs may contribute to cardiac pathology following menopause.

Evidence that renal arginine transport is impaired in spontaneously hypertensive rats

2012 ◽  
Vol 302 (12) ◽  
pp. F1554-F1562 ◽  
Author(s):  
N. W. Rajapakse ◽  
S. Kuruppu ◽  
I. Hanchapola ◽  
K. Venardos ◽  
D. L. Mattson ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Chronic Hypertension ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
No Donor ◽  
Doppler Flowmetry ◽  
Spontaneously Hypertensive ◽  
Arginine Transport ◽  
Sd Rats ◽  
No Bioavailability

Low renal nitric oxide (NO) bioavailability contributes to the development and maintenance of chronic hypertension. We investigated whether impaired l-arginine transport contributes to low renal NO bioavailability in hypertension. Responses of renal medullary perfusion and NO concentration to renal arterial infusions of the l-arginine transport inhibitor l-lysine (10 μmol·kg−1·min−1; 30 min) and subsequent superimposition of l-arginine (100 μmol·kg−1·min−1; 30 min), the NO synthase inhibitor NG-nitro-l-arginine (2.4 mg/kg; iv bolus), and the NO donor sodium nitroprusside (0.24 μg·kg−1·min−1) were examined in Sprague-Dawley rats (SD) and spontaneously hypertensive rats (SHR). Renal medullary perfusion and NO concentration were measured by laser-Doppler flowmetry and polarographically, respectively, 5.5 mm below the kidney surface. Renal medullary NO concentration was less in SHR (53 ± 3 nM) compared with SD rats (108 ± 12 nM; P = 0.004). l-Lysine tended to reduce medullary perfusion (−15 ± 7%; P = 0.07) and reduced medullary NO concentration (−9 ± 3%; P = 0.03) while subsequent superimposition of l-arginine reversed these effects of l-lysine in SD rats. In SHR, l-lysine and subsequent superimposition of l-arginine did not significantly alter medullary perfusion or NO concentration. Collectively, these data suggest that renal l-arginine transport is impaired in SHR. Renal l-[3H]arginine transport was less in SHR compared with SD rats ( P = 0.01). Accordingly, we conclude that impaired arginine transport contributes to low renal NO bioavailability observed in the SHR kidney.

scholarly journals Connecting tubule glomerular feedback mediates tubuloglomerular feedback resetting after unilateral nephrectomy

2018 ◽  
Vol 315 (4) ◽  
pp. F806-F811 ◽  
Author(s):  
Sumit R. Monu ◽  
Yilin Ren ◽  
J. X. Masjoan-Juncos ◽  
Kristopher Kutskill ◽  
Hong Wang ◽  
...  
Keyword(s):  
Indirect Measurement ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Nacl Transport ◽  
Connecting Tubule ◽  
Flow Pressure ◽  
Stop Flow ◽  
Remnant Kidney ◽  
Epithelial Sodium Channel Enac

Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure (PGC) that can cause significant glomerular injury in the remnant kidney. PGC is controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance. Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa; and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel (ENaC). Resetting of TGF post-UNx can allow systemic pressure to be transmitted to the glomerulus and cause renal damage, but the mechanism behind this resetting is unclear. Since CTGF is an Af-Art dilatory mechanism, we hypothesized that CTGF is increased after UNx and contributes to TGF resetting. To test this hypothesis, we performed UNx in Sprague-Dawley (8) rats. Twenty-four hours after surgery, we performed micropuncture of individual nephrons and measured stop-flow pressure (PSF). PSF is an indirect measurement of PGC. Maximal TGF response at 40 nl/min was 8.9 ± 1.24 mmHg in sham-UNx rats and 1.39 ± 1.02 mmHg in UNx rats, indicating TGF resetting after UNx. When CTGF was inhibited with the ENaC blocker benzamil (1 μM/l), the TGF response was 12.29 ± 2.01 mmHg in UNx rats and 13.03 ± 1.25 mmHg in sham-UNx rats, indicating restoration of the TGF responses in UNx. We conclude that enhanced CTGF contributes to TGF resetting after UNx.

Sign in / Sign up

Export Citation Format

Share Document