Abstract 266: Renovascular Remodeling in Hypertensive Dahl-SS Rats: Role of MMP Inhibitor as a Hypertension Ameliorating Agent

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sourav Kundu ◽  
Sathnur Pushpakumar ◽  
Naira Metriveli ◽  
Suresh C Tyagi ◽  
Utpal Sen
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Density ◽  
High Salt Diet ◽  
Doppler Flowmetry ◽  
Cortical Blood Flow ◽  
Mmp Inhibitor ◽  
Arterial Blood ◽  
Renal Cortical Blood Flow ◽  
Renal Vascular

High salt diet has long been associated with chronic hypertension. The development of renal injury in Dahl salt-sensitive (SS) hypertensive rats is characterized by structural and functional changes involving vascular remodeling. Increased activity of matrix metalloproteinases (MMPs) leading to alteration in the extracellular matrix (ECM) is the main mechanism contributing to increased peripheral vascular resistance. In this study, we hypothesized that inhibition of MMPs will modulate ECM remodeling by decreasing MMP activity and thus reduce mean arterial blood pressure. METHODS: We used Dahl-salt sensitive (Dahl-SS) and Lewis rats fed on high salt diet. The groups were 1) Dahl-SS, 2) Dahl-SS+GM6001 (non-specific MMP inhibitor), 3) Lewis, and 4) Lewis+GM6001. GM6001 was given at 0.5mg/mL by intra-peritoneal injection on alternate days for 3 weeks. Blood pressure, laser doppler flowmetry for renal cortical blood flow and barium angiography for renal vascular density were measured. Results: Mean arterial blood pressure was 172.10 ± 0.57 mm Hg in hypertensive Dahl-SS rats compared to 136.12 ± 1.22 mm Hg in Dahl-SS+GM6001 rats. The mean arterial pressures in lewis and lewis+GM6001 groups were 97.08 ± 0.56 and 87.63 ± 2.93 mm Hg respectively. Laser doppler flowmetry showed reduced renal cortical blood flow (1333.33 flux units) in Dahl-SS rats compared to Dahl-SS rats treated with GM6001 (1605 flux units). Lewis rats showed similar renal cortical flow with (1488.33 flux units) or without GM6001 (1425 flux units). Barium angiography demonstrated increased renal vascular density with patent branches in the renal cortex of animals treated with MMP inhibitor, GM6001. Conclusion: Our results suggest that in hypertensive Dahl-SS rats, inhibition of MMP attenuates high blood pressure, maintains patency of renal cortical vessels thus improving cortical blood flow.

Vasoactive intestinal polypeptide reduces hydrochloric acid-induced duodenal mucosal permeability

1993 ◽  
Vol 264 (2) ◽  
pp. G272-G279 ◽  
Author(s):  
O. Nylander ◽  
E. Wilander ◽  
G. M. Larson ◽  
L. Holm
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vasoactive Intestinal Polypeptide ◽  
Lesion Score ◽  
Morphological Examination ◽  
Mucosal Permeability ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
51Cr Edta ◽  
Intestinal Polypeptide

The duodenum in anesthetized rats was perfused with HCl, and mucosal integrity was assessed by measuring the clearance of 51Cr-labeled EDTA from blood to lumen and/or by morphological examination (lesion score). Duodenal blood flow was determined by laser Doppler flowmetry and luminal alkalinization as well as H+ disappearance by backtitration. Intravenous infusion of vasoactive intestinal polypeptide (VIP; 13.5 micrograms.kg-1.h-1) increased luminal alkalinization threefold and decreased clearance of 51Cr-EDTA by 50%. VIP also decreased arterial blood pressure and induced a small and irregular decrease in duodenal blood flow. Perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.1-fold, but the lesion score was not different from that in saline-perfused animals. Perfusion with 20 mM HCl increased clearance of 51Cr-EDTA four-fold and induced a greater lesion score than did 10 mM. Perfusion with either 10 or 20 mM HCl did not affect the duodenal blood flow. VIP reduced the rise in clearance of 51Cr-EDTA in response to 10 mM but not that to 20 mM HCl. Intravenous injection of prazosin (50 micrograms/kg) decreased luminal alkalinization, clearance of 51Cr-EDTA, blood pressure, and duodenal blood flow. In prazosin-pretreated rats, perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.6-fold, and the lesion score was greater in this group than in animals infused with VIP. A positive linear correlation was obtained between HCO3- secretion and the mean rate of H+ disappearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute cocaine administration alters posttraumatic blood pressure and cerebral blood flow in rats

1995 ◽  
Vol 268 (1) ◽  
pp. H68-H73
Author(s):  
J. K. Muir ◽  
E. F. Ellis
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Saline Group ◽  
Drug Abusers ◽  
Lidocaine Group ◽  
Doppler Flowmetry ◽  
Cortical Blood Flow ◽  
Group Flow

Cocaine abuse is widespread, and it is possible that its two main pharmacological actions, sympathomimetic and local anesthetic, could influence the blood pressure and cerebral blood flow response to brain injury, which occurs with increased frequency in drug abusers. We tested this hypothesis in ventilated barbiturate-anesthetized rats. Brain injury was induced using the fluid-percussion method, and cortical blood flow was measured using laser-Doppler flowmetry. Saline, cocaine, methamphetamine, or lidocaine was administered 10 min before injury. Upon injury, both cocaine- and saline-pretreated rats showed a similar acute hypertensive phase, which was followed by a period of more pronounced hypotension in the cocaine group (68 +/- 4 vs. 100 +/- 6 mmHg). Cortical blood flow increased dramatically 3–15 s following injury-induced hypertension in both the cocaine and saline groups (approximately 230-260%), but then fell below preinjury values within minutes. At 1 h postinjury, the blood flow in the saline group was 53 +/- 6% of the preinjury value, while in the cocaine group, flow was 74 +/- 7% of preinjury baseline. Similar to the cocaine-treated animals, methamphetamine also caused a more pronounced hypotensive event, but blood flow was not significantly different from saline controls. Lidocaine did not alter posttraumatic blood pressure but did significantly elevate blood flow throughout the 1-h postinjury period. At 60 min posttrauma, blood flow in the lidocaine group was 80 +/- 10% of the preinjury value. The mechanism by which cocaine alters blood pressure and blood flow after injury is not entirely certain.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Sheila Marques Fernandes ◽  
Daniel Malisani Martins ◽  
Cassiane Dezoti da Fonseca ◽  
Mirian Watanabe ◽  
Maria de Fátima Fernandes Vattimo
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Blood Flow ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Blood Flow ◽  
Arterial Blood ◽  
Chronic Hyperglycemia ◽  
Iodinated Contrast ◽  
Renal Vascular

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulinclearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulinclearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

Circadian periodicity of cerebral blood flow revealed by laser-Doppler flowmetry in awake rats: relation to blood pressure and activity

2005 ◽  
Vol 289 (4) ◽  
pp. H1662-H1668 ◽  
Author(s):  
C. A. Wauschkuhn ◽  
K. Witte ◽  
S. Gorbey ◽  
B. Lemmer ◽  
L. Schilling
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Locomotor Activity ◽  
Cerebral Perfusion ◽  
Circadian Variation ◽  
Laser Doppler ◽  
Doppler Flowmetry ◽  
Circadian Periodicity ◽  
Arterial Blood

Cardiovascular parameters such as arterial blood pressure (ABP) and heart rate display pronounced circadian variation. The present study was performed to detect whether there is a circadian periodicity in the regulation of cerebral perfusion. Normotensive Sprague-Dawley rats (SDR, ∼15 wk old) and hypertensive (mREN2)27 transgenic rats (TGR, ∼12 wk old) were instrumented in the abdominal aorta with a blood pressure sensor coupled to a telemetry system for continuous recording of ABP, heart rate, and locomotor activity. After 5–12 days, a laser-Doppler flow (LDF) probe was attached to the skull by means of a guiding device to measure changes in brain cortical blood flow (CBF). After the animals recovered from anesthesia, measurements were taken for 3–4 days. The time series were analyzed with respect to the midline estimating statistic of rhythm (i.e., mean value of a periodic event after fit to a cosine function), amplitude, and acrophase (i.e., phase angle that corresponds to the peak of a given period) of the 24-h period. The LDF signal displayed a significant circadian rhythm, with the peak occurring at around midnight in SDR and TGR, despite inverse periodicity of ABP in TGR. This finding suggests independence of LDF periodicity from ABP regulation. Furthermore, the acrophase of the LDF was consistently found before the acrophase of the activity. From the present data, it is concluded that there is a circadian periodicity in the regulation of cerebral perfusion that is independent of circadian changes in ABP and probably is also independent of locomotor activity. The presence of a circadian periodicity in CBF may have implications for the occurrence of diurnal alterations in cerebrovascular events in humans.

Renal Vascular Responses to Dopamine: Haemodynamic and Angiographic Observations in Normal Man

1973 ◽  
Vol 45 (6) ◽  
pp. 733-742 ◽  
Author(s):  
N. K. Hollenberg ◽  
D. F. Adams ◽  
P. Mendell ◽  
H. L. Abrams ◽  
J. P. Merrill
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Arterial Blood Pressure ◽  
Vascular Resistance ◽  
Cardiovascular Effects ◽  
Normal Subjects ◽  
Vascular Effects ◽  
Arterial Blood ◽  
Normal Man ◽  
Renal Vascular

1. The renal vascular response to intravenously administered dopamine was assessed in normal man by selective renal arteriography and xenon washout. Infusion of 3 μg min−1 kg−1 induced renal vasodilatation with an increase in the cortical component of blood flow. Arterial blood pressure was not influenced and a systemic effect was not demonstrable. Lower doses did not induce a renal response. Increasing dosage raised arterial blood pressure and induced subjective symptoms, but did not result in a further increase in renal blood flow. 2. Renal vascular resistance increased with increasing age in the normal subjects. A significant inverse relationship was found between the initial vascular resistance and the renal vasodilator response to dopamine. It thus appears that the vascular effects of increasing age (nephrosclerosis) may limit the dilator response to dopamine. 3. It is concluded that dopamine is an effective renal cortical vasodilator when administered intravenously at doses which are free from other systemic cardiovascular effects. The dose-response relationship must be considered in attempts at reversal of conditions characterized by renal vasoconstriction.

Renal vascular effects of epinephrine infusion in the halothane-anesthetized piglet

1994 ◽  
Vol 72 (4) ◽  
pp. 394-396 ◽  
Author(s):  
Keith J. Harrington ◽  
Robert G. Allen ◽  
Jay W. Dewald
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Arterial Blood Pressure ◽  
Vascular Resistance ◽  
Mean Arterial Blood Pressure ◽  
Renal Vascular Resistance ◽  
Epinephrine Infusion ◽  
Arterial Blood ◽  
Renal Vascular

The objective of this study was to determine the dose–response effects of epinephrine, given by systemic intravenous infusion to the halothane-anesthetized newborn piglet, on renal blood flow, mean arterial blood pressure, and renal vascular resistance. Seven newborn piglets were acutely instrumented. A transit-time ultrasound flow probe was placed around the renal artery and a femoral arterial catheter was placed for blood pressure monitoring. Epinephrine was infused in doubling doses from 0.2 to 3.2 μg∙kg−1∙min−1. Mean arterial blood pressure increased from 54 mmHg (1 mmHg = 133.3 Pa) to an average of 96 mmHg at 3.2 μg∙kg−1∙min−1 of epinephrine. Renal blood flow increased from 165 mL∙min−1∙100 g−1 at baseline to 185 mL∙min−1∙100 g−1 at a dose of 0.2 μg∙kg−1∙min−1 and increased further at 0.4 and 0.8 μg∙kg−1∙min−1 to reach 261 mL∙min−1∙100 g−1. Renal blood flow began to fall at a dose of 3.2 μg∙kg−1∙min−1, remaining however, significantly above baseline (211 mL∙min−1∙100 g−1). Consequently, calculated renal vascular resistance fell as the dose was increased from 0.2 to 0.8 μg∙kg−1∙min−1 and then rose again at 1.6 and 3.2 μg∙kg−1∙min−1, being significantly above baseline at 3.2 μg∙kg−1∙min−1. These results demonstrate that epinephrine when given by systemic infusion to the halothane-anesthetized newborn pig is a renal vasodilator at low doses and causes renal vasoconstriction at moderate to high doses. Renal blood flow remained above baseline at all doses tested, and thus, within the dosage range tested, epinephrine infusion should not cause renal ischemia.Key words: epinephrine, kidney blood flow, piglet, renal vascular resistance.

Duodenal mucosal alkaline secretion, permeability, and blood flow

1993 ◽  
Vol 265 (6) ◽  
pp. G1029-G1038 ◽  
Author(s):  
O. Nylander ◽  
A. Hallgren ◽  
L. Holm
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Arterial Blood Pressure ◽  
Fluid Secretion ◽  
Duodenal Mucosa ◽  
Water Soluble ◽  
Mucosal Permeability ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
Alkaline Secretion

The relationship between duodenal mucosal alkaline secretion, permeability, and blood flow was examined in anesthetized rats. Duodenum was perfused with saline, and rate of luminal alkalinization (LA), mucosal permeability (clearance of 51Cr-EDTA from blood to lumen), effluent volume, mean arterial blood pressure (MABP), and blood flow (laser-Doppler flowmetry) were determined. Infusion of vasoactive intestinal polypeptide (VIP, 13.5 micrograms.kg-1 x h-1 i.v.) increased LA and fluid secretion but decreased MABP and mucosal permeability. The concentration of base in the secreted fluid was 45 mM. Systemic infusion of VIP (2.5 micrograms.kg-1 x h-1) increased LA and fluid secretion; the HCO3- concentration in secreted fluid was 86 mM. The lower VIP dose affected neither blood flow nor mucosal permeability. Both intravenous (10 mg/kg + 3 mg.kg-1 x h-1) and intraluminal (3 x 10(-3) M) N omega-nitro-L-arginine (L-NNA) increased LA and effluent volume; the HCO3- concentration in the secreted fluid was 38 and 44 mM, respectively. Intravenous, but not intraluminal, L-NNA increased mucosal permeability and decreased blood flow. Reduction of arterial blood pressure by blood withdrawal or by injection of prazosin (50 micrograms/kg i.v.) or hexamethonium (20 mg/kg i.v.) decreased LA and mucosal permeability. Prazosin decreased blood flow, whereas hexamethonium slightly increased blood flow. We conclude that NO may be an inhibitory regulator of LA and that both L-NNA and VIP increase LA via stimulation of active HCO3- transport. VIP probably increases HCO3- and fluid secretion by two separate ion transport mechanisms. No causal relationship exists between LA and blood flow, between LA and mucosal permeability, or between mucosal permeability and blood flow. A positive linear correlation exists between MABP and mucosal permeability, suggesting that marked changes of MABP may influence permeation of small water-soluble solutes across duodenal mucosa.

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