Angiotensin II (ANG II), renal perfusion pressure (RPP) and synchronization of cortical blood flow studied using laser speckle perfusion imaging (LSPI)

An adaptation of the in vitro perfused hydronephrotic rat kidney model allowing in situ measurement of arteriolar membrane potentials is described. At a renal perfusion pressure of 80 mmHg, resting membrane potentials of interlobular arteries (22 +/- 2 microns) and afferent (14 +/- 1 microns) and efferent arterioles (12 +/- 1 microns) were -40 +/- 2 (n = 8), -40 +/- 1 (n = 45), and -38 +/- 2 mV (n = 22), respectively (P = 0.75). Using a dual-pipette system to stabilize the impalement site, we measured afferent and efferent arteriolar membrane potentials during angiotensin II (ANG II)-induced vasoconstriction. ANG II (0.1 nM) reduced afferent arteriolar diameters from 13 +/- 1 to 8 +/- 1 microns (n = 8, P = 0.005) and membrane potentials from -40 +/- 2 to -29 +/- mV (P = 0.012). ANG II elicited a similar vasoconstriction in efferent arterioles, decreasing diameters from 13 +/- 1 to 8 +/- 1 microns (n = 8, P = 0.004), but failed to elicit a significant depolarization (-39 +/- 2 for control; -36 +/- 3 mV for ANG II; P = 0.27). Our findings thus indicate that resting membrane potentials of pre- and postglomerular arterioles are similar and lie near the threshold activation potential for L-type Ca channels. ANG II-induced vasoconstriction appears to be closely coupled to membrane depolarization in the afferent arteriole, whereas mechanical and electrical responses appear to be dissociated in the efferent arteriole.

Download Full-text

Purinergic P2X1 receptor, purinergic P2X7 receptor, and angiotensin II type 1 receptor interactions in the regulation of renal afferent arterioles in angiotensin II-dependent hypertension

AJP Renal Physiology ◽

10.1152/ajprenal.00602.2019 ◽

2020 ◽

Vol 318 (6) ◽

pp. F1400-F1408 ◽

Cited By ~ 1

Author(s):

Supaporn Kulthinee ◽

Weijian Shao ◽

Martha Franco ◽

L. Gabriel Navar

Keyword(s):

Angiotensin Ii ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Ang Ii ◽

Renal Perfusion Pressure ◽

Arteriolar Resistance ◽

Purinergic P2x7 Receptor ◽

Afferent Arterioles ◽

Purinergic P2x Receptors

In ANG II-dependent hypertension, ANG II activates ANG II type 1 receptors (AT1Rs), elevating blood pressure and increasing renal afferent arteriolar resistance (AAR). The increased arterial pressure augments interstitial ATP concentrations activating purinergic P2X receptors (P2XRs) also increasing AAR. Interestingly, P2X1R and P2X7R inhibition reduces AAR to the normal range, raising the conundrum regarding the apparent disappearance of AT1R influence. To evaluate the interactions between P2XRs and AT1Rs in mediating the increased AAR elicited by chronic ANG II infusions, experiments using the isolated blood perfused juxtamedullary nephron preparation allowed visualization of afferent arteriolar diameters (AAD). Normotensive and ANG II-infused hypertensive rats showed AAD responses to increases in renal perfusion pressure from 100 to 140 mmHg by decreasing AAD by 26 ± 10% and 19 ± 4%. Superfusion with the inhibitor P2X1Ri (NF4490; 1 μM) increased AAD. In normotensive kidneys, superfusion with ANG II (1 nM) decreased AAD by 16 ± 4% and decreased further by 19 ± 5% with an increase in renal perfusion pressure. Treatment with P2X1Ri increased AAD by 30 ± 6% to values higher than those at 100 mmHg plus ANG II. In hypertensive kidneys, the inhibitor AT1Ri (SML1394; 1 μM) increased AAD by 10 ± 7%. In contrast, treatment with P2X1Ri increased AAD by 21 ± 14%; combination with P2X1Ri plus P2X7Ri (A438079; 1 μM) increased AAD further by 25 ± 8%. The results indicate that P2X1R, P2X7R, and AT1R actions converge at receptor or postreceptor signaling pathways, but P2XR exerts a dominant influence abrogating the actions of AT1Rs on AAR in ANG II-dependent hypertension.

Download Full-text

Effect of interactions between nitric oxide and angiotensin II on pressure diuresis and natriuresis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.5.r1676 ◽

1997 ◽

Vol 273 (5) ◽

pp. R1676-R1682 ◽

Cited By ~ 8

Author(s):

María Isabel Madrid ◽

Miguel García-Salom ◽

Jerónimo Tornel ◽

Marc De Gasparo ◽

Francisco J. Fenoy

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Renal Function ◽

Angiotensin Ii ◽

Methyl Ester ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Angiotensin Receptors ◽

Water Excretion ◽

Renal Perfusion Pressure

The present study examined the effect of an angiotensin II AT1 or AT2 receptor antagonist on the impairment of the pressure diuresis and natriuresis response produced by nitric oxide (NO) synthesis blockade. N ω-nitro-l-arginine methyl ester (l-NAME, 37 nmol ⋅ kg−1 ⋅ min−1) lowered renal blood flow and reduced the slopes of the pressure diuresis and natriuresis responses by 44 and 40%, respectively. Blockade of AT1 receptors with valsartan increased slightly sodium and water excretion at low renal perfusion pressure (RPP). Blockade of AT2 receptors with PD-123319 had no effect on renal function. The administration of valsartan or PD-123319 to rats given l-NAME had no effect on the renal vasocontriction induced by NO synthesis blockade. In addition, in rats givenl-NAME, valsartan elevated baseline excretory values at all RPP studied, but it had no effect on the sensitivity of the pressure diuresis and natriuresis response. However, the administration of PD-123319 tol-NAME-pretreated rats shifted the slopes of the pressure diuresis and natriuresis responses toward control values, indicating that the impairment produced by NO synthesis blockade on pressure diuresis is dependent on the activation of AT2 angiotensin receptors.

Download Full-text

Cortical and medullary hemodynamics in deoxycorticosterone acetate-salt hypertensive mice.

Journal of the American Society of Nephrology ◽

10.1681/asn.v93346 ◽

1998 ◽

Vol 9 (3) ◽

pp. 346-354 ◽

Cited By ~ 1

Author(s):

V Gross ◽

A Lippoldt ◽

J Bohlender ◽

M Bader ◽

A Hansson ◽

...

Keyword(s):

Blood Flow ◽

Volume Expansion ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Kidney Weight ◽

Cortical Blood Flow ◽

Renal Perfusion Pressure ◽

Medullary Blood Flow ◽

Saline Loading ◽

Baseline Values

The effect of acutely increasing renal perfusion pressure or extracellular fluid volume on renal medullary and cortical blood flow was examined in the low-renin deoxycorticosterone acetate (DOCA)-salt hypertension model in mice. A 50-mg DOCA tablet was implanted, and 1% saline was given as drinking water for 3 wk. Medullary and cortical blood flow were determined with laser-Doppler flowmetry, and whole-kidney blood flow was measured with a transit-time ultrasound flowprobe around the renal artery. In control mice, total renal blood flow ranged from 6.3 and 7.6 ml/min per g kidney weight and in DOCA-salt mice from 4.3 and 4.7 ml/min per g kidney weight, respectively, and was minimally affected as renal perfusion pressure was increased. Renal vascular resistance increased correspondingly. During stepwise increases in renal artery pressure from 90 to 140 mmHg, medullary blood flow progressively increased in control mice to 125% of baseline values, whereas cortical blood flow did not change. In DOCA-salt mice, increasing BP from 100 to 154 mmHg had no effect on either cortical or medullary blood flow. Urine flow and sodium excretion were lower in DOCA-salt mice than in controls and increased nearly to the same extent in both groups after volume expansion with isotonic saline. Total renal blood flow increased after saline loading, more in controls than in DOCA-salt mice. Increases in medullary blood flow after saline loading were up to 122% of baseline values in controls and demonstrated a significantly steeper slope than the 110% of baseline increases in DOCA-salt mice. Cortical blood flow, however, was not different between the groups. Thus, medullary blood flow is not as tightly autoregulated as cortical blood flow in normal mice. Natriuresis with acute volume loading is facilitated by increased medullary blood flow. In DOCA-salt mice, the medullary blood flow reaction to renal perfusion pressure increases is abolished, whereas flow increases with extracellular volume expansion are diminished. These results suggest that diminished pressure-natriuresis responses in DOCA-salt mice are related to perturbed medullary blood flow.

Download Full-text

Relationship between renal perfusion pressure and blood flow in different regions of the kidney

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.264.3.r578 ◽

1993 ◽

Vol 264 (3) ◽

pp. R578-R583 ◽

Cited By ~ 45

Author(s):

D. L. Mattson ◽

S. Lu ◽

R. J. Roman ◽

A. W. Cowley

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Laser Doppler Flowmetry ◽

Renal Cortex ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Doppler Flowmetry ◽

Cortical Blood Flow ◽

Renal Perfusion Pressure ◽

Medullary Blood Flow

The present study examined the autoregulation of blood flow in different regions of the renal cortex and medulla in volume-expanded or hydropenic anesthetized rats. Blood flow was measured in the whole kidney by electromagnetic flowmetry, in the superficial cortex with implanted fibers and external probes for laser-Doppler flowmetry, and in the deep cortex and inner and outer medulla with implanted fibers for laser-Doppler flowmetry. At renal perfusion pressure > 100 mmHg, renal blood flow, superficial cortical blood flow, and deep cortical blood flow were all very well autoregulated in both volume-expanded and hydropenic rats. Inner and outer medullary blood flow were also well autoregulated in hydropenia, but blood flow in these regions was very poorly autoregulated in volume-expanded animals. As renal perfusion pressure was decreased below 100 mmHg in volume-expanded and hydropenic animals, renal blood flow, superficial and deep cortical blood flow, and inner and outer medullary blood flow all decreased. The results of these experiments demonstrate that blood flow in both the inner and outer portions of the renal medulla of the kidney is poorly autoregulated in volume-expanded rats but well autoregulated in hydropenic animals. In contrast, blood flow in all regions of the renal cortex is well autoregulated in both volume-expanded and hydropenic animals. These results suggest that changes in resistance in the postglomerular circulation of deep nephrons are responsible for the poor autoregulation of medullary blood flow in volume expansion despite well autoregulated cortical blood flow.

Download Full-text

Renal Perfusion Pressure Determines Infiltration of Leukocytes in the Kidney of Rats With Angiotensin II–Induced Hypertension

Hypertension ◽

10.1161/hypertensionaha.120.15295 ◽

2020 ◽

Vol 76 (3) ◽

pp. 849-858 ◽

Cited By ~ 1

Author(s):

Satoshi Shimada ◽

Justine M. Abais-Battad ◽

Ammar J. Alsheikh ◽

Chun Yang ◽

Megan Stumpf ◽

...

Keyword(s):

Angiotensin Ii ◽

Perfusion Pressure ◽

Left Kidney ◽

Renal Perfusion ◽

Leukocyte Infiltration ◽

Ang Ii ◽

Dietary Salt ◽

Renal Perfusion Pressure ◽

Induced Hypertension ◽

The Right

The present study examined the extent to which leukocyte infiltration into the kidneys in Ang II (angiotensin II)-induced hypertension is determined by elevation of renal perfusion pressure (RPP). Male Sprague-Dawley rats were instrumented with carotid and femoral arterial catheters for continuous monitoring of blood pressure and a femoral venous catheter for infusion. An inflatable aortic occluder cuff placed between the renal arteries with computer-driven servo-controller maintained RPP to the left kidney at control levels during 7 days of intravenous Ang II (50 ng/kg per minute) or vehicle (saline) infusion. Rats were fed a 0.4% NaCl diet throughout the study. Ang II–infused rats exhibited nearly a 50 mm Hg increase of RPP (carotid catheter) to the right kidney while RPP to the left kidney (femoral catheter) was controlled at baseline pressure throughout the study. As determined at the end of the studies by flow cytometry, right kidneys exhibited significantly greater numbers of T cells, B cells, and monocytes/macrophages compared with the servo-controlled left kidneys and compared with vehicle treated rats. No difference was found between Ang II servo-controlled left kidneys and vehicle treated kidneys. Immunostaining found that the density of glomeruli, cortical, and outer medullary capillaries were significantly reduced in the right kidney of Ang II–infused rats compared with servo-controlled left kidney. We conclude that in this model of hypertension the elevation of RPP, not Ang II nor dietary salt, leads to leukocyte infiltration in the kidney and to capillary rarefaction.

Download Full-text

Direct measurement of renal medullary blood flow in the dog

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.267.1.r253 ◽

1994 ◽

Vol 267 (1) ◽

pp. R253-R259 ◽

Cited By ~ 5

Author(s):

D. M. Strick ◽

M. J. Fiksen-Olsen ◽

J. C. Lockhart ◽

R. J. Roman ◽

J. C. Romero

Keyword(s):

Blood Flow ◽

Pressure Range ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Flow Probe ◽

Renal Autoregulation ◽

Renal Perfusion Pressure ◽

Medullary Blood Flow ◽

Renal Medullary Blood Flow ◽

Doppler Flowmeter

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)

Download Full-text

Renal perfusion pressure and renin secretion in bilaterally renal denervated sheep

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-111 ◽

1994 ◽

Vol 72 (7) ◽

pp. 782-787 ◽

Cited By ~ 10

Author(s):

L. Fan ◽

S. Mukaddam-Daher ◽

J. Gutkowska ◽

B. S. Nuwayhid ◽

E. W. Quillen Jr.

Keyword(s):

Angiotensin Ii ◽

Atrial Natriuretic Factor ◽

Perfusion Pressure ◽

Excretion Rate ◽

Plasma Renin ◽

Renal Perfusion ◽

Renin Secretion ◽

Renal Nerves ◽

Renal Perfusion Pressure ◽

Plasma Angiotensin

To further investigate the influence of renal nerves on renin secretion, the renin secretion responses to step reductions of renal perfusion pressure (RPP) were studied in conscious sheep with innervated kidneys (n = 5) and with bilaterally denervated kidneys (n = 5). The average basal level of RPP in sheep with denervated kidneys (82 ± 4 mmHg; 1 mmHg = 133.3 Pa) was similar to that in sheep with innervated kidneys (83 ± 3 mmHg). RPP was reduced in four sequential 15-min steps, to a final level of 54 ± 2 mmHg in sheep with innervated kidneys and to 57 ± 1 mmHg in denervated sheep. The renin secretion rate was increased as RPP was reduced in sheep with innervated kidneys. Baseline peripheral plasma renin activity was reduced and there was almost no response of renin secretion rate to reduction of RPP in sheep with denervated kidneys. Also, baseline renal blood flow, urine flow rate, sodium excretion rate, and potassium excretion rate were higher in sheep with denervated kidneys than those with innervated kidneys. Baseline plasma angiotensin II was similar in both groups of sheep. As RPP was decreased, plasma angiotensin II was increased in sheep with innervated kidneys, but was not significantly altered in sheep with denervated kidneys. Plasma atrial natriuretic factor was unaltered by either reduction of RPP or renal denervation. In conclusion, hormonal factors, such as angiotensin II and atrial natriuretic factor, do not account for the dramatic suppression of renin secretion in response to the reduction of RPP in sheep with bilateral renal denervation. Renal nerves are a necessary component in the control of renin secretion during reduction of RPP and may contribute to the regulation of baseline plasma renin activity and sodium excretion rate in conscious ewes.Key words: renin secretion, renal perfusion pressure, renal nerves, denervation, sheep.

Download Full-text

Autoregulation of renal blood flow in the puppy

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1975.229.4.983 ◽

1975 ◽

Vol 229 (4) ◽

pp. 983-988 ◽

Cited By ~ 43

Author(s):

PA Jose ◽

LM Slotkoff ◽

S Montgomery ◽

PL Calcagno ◽

G Eisner

Keyword(s):

Blood Flow ◽

Angiotensin Ii ◽

Renal Blood Flow ◽

Perfusion Pressure ◽

Electromagnetic Flowmeter ◽

Renin Angiotensin System ◽

Renal Perfusion ◽

Angiotensin System ◽

Group Of Seven ◽

Selective Blockade

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.

Download Full-text

Mechanism of intrarenal blood flow redistribution after carotid artery occlusion

AJP Renal Physiology ◽

10.1152/ajprenal.1977.232.2.f167 ◽

1977 ◽

Vol 232 (2) ◽

pp. F167-F172 ◽

Cited By ~ 1

Author(s):

E. H. Prosnitz ◽

E. J. Zambraski ◽

G. F. DiBona

Keyword(s):

Blood Flow ◽

Carotid Artery ◽

Renal Blood Flow ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Artery Occlusion ◽

Carotid Artery Occlusion ◽

Outer Cortex ◽

Renal Sympathetic Nerve Activity ◽

Renal Perfusion Pressure

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.

Download Full-text