scholarly journals Hemodynamic phenotyping of transgenic rats with ubiquitous expression of an angiotensin-(1-7)-producing fusion protein

2021 ◽  
Author(s):  
Daniele T Alves ◽  
Luiz F Mendes ◽  
Walkyria Oliveira Sampaio ◽  
Leda Maria de Castro Coimbra Campos ◽  
Maria Aparecida R Vieira ◽  
...  
Keyword(s):  
Blood Flow ◽  
Fusion Protein ◽  
Regional Blood Flow ◽  
Peripheral Resistance ◽  
Free Water ◽  
Renin Angiotensin System ◽  
Sodium Concentration ◽  
Tissue Expression ◽  
Transgenic Rat ◽  
Free Water Clearance

Activation of the angiotensin (Ang) converting enzyme 2/Ang-(1-7)/MAS receptor pathway of the renin-angiotensin system induces protective mechanisms in different diseases.  Herein, we describe the cardiovascular phenotype of a new transgenic rat line (TG7371) that expresses an Ang-(1-7)-producing fusion protein.  The transgene-specific mRNA and the corresponding protein were shown to be present in all evaluated tissues of TG7371 with the highest expression in aorta and brain.  Plasma Ang-(1-7) levels, measured by radioimmunoassay were similar to control SD rats, however high Ang-(1-7) levels were found in the hypothalamus.  TG7371 showed lower baseline mean arterial pressure, assessed in conscious or anesthetized rats by telemetry or short-term recordings, associated with increased plasma ANP and higher urinary sodium concentration.  Evaluation of regional blood flow and hemodynamic parameters with fluorescent microspheres showed a significant increase in blood flow in different tissues (kidneys, mesentery, muscle, spleen, brown fat, heart and skin), with a resulting decreased total peripheral resistance.  TG7371 rats also presented increased cardiac and global sympathetic tone, increased plasma AVP levels and decreased free water clearance.  Altogether, our data show that expression of an Ang-(1-7)-producing fusion protein induced a hypotensive phenotype due to widespread vasodilation and consequent fall in peripheral resistance.  This phenotype was associated with an increase in ANP together with an increase in AVP and sympathetic drive, which did not fully compensate the lower BP.  Here we present the hemodynamic impact of long-term increase in tissue expression of an Ang-(1-7)-fusion protein and provide a new tool to investigate this peptide in different pathophysiological conditions.

Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance

2007 ◽  
Vol 292 (5) ◽  
pp. H2485-H2490 ◽  
Author(s):  
Giancarla A. Botelho-Santos ◽  
Walkyria O. Sampaio ◽  
Timothy L. Reudelhuber ◽  
Michael Bader ◽  
Maria J. Campagnole-Santos ◽  
...  
Keyword(s):  
Stroke Volume ◽  
Fusion Protein ◽  
Vascular Resistance ◽  
Regional Blood Flow ◽  
Peripheral Resistance ◽  
Physiological Role ◽  
Transgenic Rat ◽  
Fat Tissue ◽  
Transgenic Rats ◽  
Hemodynamic Measurements

We have described a transgenic rat line that expresses an angiotensin-(1-7)-producing fusion protein, the TGR(A1-7)3292. In these rats, testis acts as an angiotensin-(1-7) biological pump, increasing its plasma concentration 2.5-fold. In this study, we performed hemodynamic measurements in TGR(A1-7)3292 and age-matched Hannover Sprague-Dawley (SD) control rats, using fluorescent microspheres. Urethane-anesthetized transgenic rats had similar levels of baseline blood pressure (99 ± 3 mmHg) as did SD rats (101 ± 3 mmHg). However, pronounced differences were observed in other hemodynamic measurements. TGR(A1-7)3292 rats presented a significant increase in stroke volume (0.29 ± 0.01 vs. 0.25 ± 0.01 ml in SD), increased cardiac index (24.6 ± 0.91 vs. 21.9 ± 0.65 ml·min−1·kg) and decreased total peripheral resistance (3.9 ± 0.13 vs. 4.5 ± 0.13 mmHg·ml−1·min·100 g). The increase in stroke volume in transgenic rats may be partially explained by the small decrease in heart rate (326 ± 7.0 vs. 359 ± 6.0 beats/min in SD). Strikingly, TGR(A1-7)3292 rats presented a substantial decrease in the vascular resistance in lung, spleen, kidney, adrenals, brain, testis and brown fat tissue with no significant differences in the left ventricle, mesentery, skin, gastrocnemius muscle and white fat tissue. These results corroborate and extend previous results observed after acute angiotensin-(1-7) infusion, showing that chronic increase in circulating angiotensin-(1-7) produces sustained and important changes in regional and systemic hemodynamics. Moreover, our data suggest a physiological role for angiotensin-(1-7) in the tonic control of regional blood flow.

Effect of vasopressin antagonist and saralasin on regional blood flow following hemorrhage

1983 ◽  
Vol 245 (5) ◽  
pp. H749-H755
Author(s):  
C. C. Pang
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Peripheral Resistance ◽  
Renin Angiotensin System ◽  
Peripheral Circulation ◽  
Angiotensin System ◽  
Vasopressin Antagonist ◽  
Renin Angiotensin ◽  
Radioactive Microsphere ◽  
Anesthetized Rats

The effects of hemorrhagic hypotension on mean arterial pressure (MAP), cardiac output (CO), and its distribution were investigated in halothane-anesthetized rats using the radioactive microsphere technique. Hemorrhage (12 ml/kg) decreased MAP and CO, increased total peripheral resistance (TPR), and decreased blood flow (BF) to the heart, stomach, intestine, kidneys, skin, cecum, and colon. The effects of antagonists of vasopressin and the renin-angiotensin system on peripheral circulation following hypotensive hemorrhage were also examined using d(CH2)5Tyr(Me)AVP and saralasin, respectively. Injection of the vasopressin antagonist caused a reduction of MAP by reducing TPR and caused an increase of percent distribution of CO to the stomach, skin, cecum, and colon. Intravenous infusion of saralasin caused significant reductions of MAP by reducing TPR. Saralasin caused an increase of percent distribution of CO to the kidneys. The results show that both vasopressin and the renin-angiotensin systems participate in the control of MAP and peripheral vascular resistance following hypotensive hemorrhage in anesthetized rats.

Sexual dimorphism in regional blood flow responses to vasopressin in conscious rats

1997 ◽  
Vol 273 (3) ◽  
pp. R1126-R1131 ◽  
Author(s):  
Y. X. Wang ◽  
J. T. Crofton ◽  
S. L. Bealer ◽  
L. Share
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Regional Blood Flow ◽  
Pressor Response ◽  
Peripheral Resistance ◽  
Female Rats ◽  
Sexually Dimorphic ◽  
Arterial Blood ◽  
Vasoconstrictor Response ◽  
Renal Vascular

The greater pressor response to vasopressin in male than in nonestrous female rats results from a greater increase in total peripheral resistance in males. The present study was performed to identify the vascular beds that contribute to this difference. Mean arterial blood pressure (MABP) and changes in blood flow in the mesenteric and renal arteries and terminal aorta were measured in conscious male and nonestrous female rats 3 h after surgery. Graded intravenous infusions of vasopressin induced greater increases in MABP and mesenteric vascular resistance and a greater decrease in mesenteric blood flow in males. Vasopressin also increased renal vascular resistance to a greater extent in males. Because renal blood flow remained unchanged, this difference may be due to autoregulation. The vasopressin-induced reduction in blood flow and increased resistance in the hindquarters were moderate and did not differ between sexes. Thus the greater vasoconstrictor response to vasopressin in the mesenteric vascular bed of male than nonestrous females contributed importantly to the sexually dimorphic pressor response to vasopressin in these experiments.

Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs

1988 ◽  
Vol 255 (6) ◽  
pp. R1064-R1068 ◽  
Author(s):  
K. L. Goetz ◽  
B. C. Wang ◽  
J. B. Madwed ◽  
J. L. Zhu ◽  
R. J. Leadley
Keyword(s):  
Vascular Endothelial Cells ◽  
Peripheral Resistance ◽  
Free Water ◽  
Urine Osmolality ◽  
Urinary Sodium Excretion ◽  
Conscious Dogs ◽  
Plasma Norepinephrine ◽  
Vascular Endothelial ◽  
Free Water Clearance ◽  
Physiological Processes

Endothelin is a recently discovered vasoconstrictor peptide that is synthesized in certain vascular endothelial cells. We have identified the cardiovascular, renal, and hormonal responses that can be elicited in conscious dogs by intravenous administration of endothelin at rates of 10 and 30 ng.kg-1.min-1 for 60 min (0.24 and 0.72 nmol.kg-1/1-h infusion). Each dose of endothelin increased total peripheral resistance, arterial pressure, and left atrial pressure and decreased heart rate and cardiac output. Hematocrit increased by 4.8% (NS) and 22.9% (P less than 0.01) in response to the lower and higher infusion rates, respectively. Urinary sodium excretion, urine osmolality, and osmolar clearance decreased and free water clearance increased. The lower dose of endothelin decreased plasma norepinephrine and increased plasma atriopeptin. The higher dose increased plasma levels of vasopressin, renin, aldosterone, norepinephrine, epinephrine, and atriopeptin. The higher infusion rate of the peptide caused one or more brief vomiting episodes in four of five dogs. Although it is not yet known whether endothelin is a circulating hormone, it is clear that this peptide is capable of causing profound cardiovascular, renal, and endocrine alterations in conscious dogs. The possible relevance of these observations to physiological processes and to pathological conditions such as hypertension remains to be established.

Oestrogen-induced changes in renal haemodynamics in the rat: Influence of plasma and intrarenal renin

1986 ◽  
Vol 71 (5) ◽  
pp. 613-619 ◽  
Author(s):  
Mr J. K. Evans ◽  
P. F. Naish ◽  
G. M. Aber
Keyword(s):  
Blood Flow ◽  
Plasma Renin Activity ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Peripheral Resistance ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renal Haemodynamics ◽  
Renin Activity ◽  
Female Rats

1. The effect of oestrone acetate (in total doses of 5 and 10 mg) on systemic and renal haemodynamics and the renin-angiotensin system has been studied in adult female rats. 2. The administration of 10 mg of oestrogen resulted in a significant fall in renal blood flow associated with significant rises in both renal vascular resistance and mean arterial pressure. No changes were noted in cardiac output or total peripheral resistance at either dose. 3. Whilst the higher dose of oestrogen induced a significant increase in plasma renin activity, no change was noted in animals receiving 5 mg of oestrogen. Both regimens caused significant reductions in plasma and intrarenal renin concentrations. 4. Although renal blood flow correlated with plasma renin activity in animals with a normal renal blood flow, no such correlation was noted in animals with oestrogen-induced reductions in renal blood flow. 5. The present study demonstrates that oestrogen-induced reductions in renal blood flow result from a rise in intrarenal vascular resistance which cannot be accounted for by simultaneous changes in either plasma renin activity or renal renin concentration.

scholarly journals Age and renal prostaglandin inhibition during exercise and heat stress

1999 ◽  
Vol 86 (6) ◽  
pp. 1936-1943 ◽  
Author(s):  
W. B. Farquhar ◽  
W. L. Kenney
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Acute Exercise ◽  
Free Water ◽  
Placebo Control ◽  
Free Water Clearance ◽  
Urine Production

Aging is associated with a number of physiological changes that may cause the kidney to rely to a greater extent on vasodilatory PGs for normal functioning. Acute exercise has been shown to cause renal vasoconstriction that may be partially buffered by vasodilatory PGs. To determine the relative importance of renal PGs during exercise in older adults, we compared the renal effects of the PG inhibitor ibuprofen (1.2 g/day for 3 days) vs. a placebo control in a cohort of eight younger (24 ± 2 yr) and eight older (64 ± 2 yr) women during treadmill exercise (∼57% maximal oxygen consumption) in the heat (36°C). This over-the-counter dose of ibuprofen reduced renal PG (i.e., PGE2) excretion by 47% ( P < 0.05). Acute exercise in the heat caused dramatic decreases in glomerular filtration rate, renal blood flow, and sodium excretion in both age groups. PG inhibition was associated with greater decreases in urine production and free water clearance ( P < 0.05). There were no drug-related declines in glomerular filtration rate or renal blood flow. We conclude that PG inhibition has only modest effects on renal function during exercise. Also, the lack of hemodynamic changes with PG inhibition indicates that healthy well-hydrated older women are not in a renal PG-dependent state.

Changes in regional blood flow distribution and oxygen supply during hypoxia in conscious rats

1993 ◽  
Vol 74 (1) ◽  
pp. 211-214 ◽  
Author(s):  
I. Kuwahira ◽  
N. C. Gonzalez ◽  
N. Heisler ◽  
J. Piiper
Keyword(s):  
Blood Flow ◽  
Oxygen Supply ◽  
Regional Blood Flow ◽  
Acute Hypoxia ◽  
Peripheral Resistance ◽  
Respiratory Muscles ◽  
Flow Distribution ◽  
Aortic Blood Flow ◽  
Aortic Blood ◽  
O2 Concentration

The effects of acute hypoxia on central hemodynamics, regional blood flow, and regional oxygen supply (blood flow x arterial O2 concentration) were studied in conscious resting rats. Regional blood flow was determined by the radiolabeled microsphere technique. Blood pressure, heart rate; and aortic blood flow increased and total peripheral resistance decreased significantly during hypoxia. Blood flow to brain, respiratory muscles, and liver increased both in absolute value and as a fraction of the aortic blood flow. Fractional blood flow to the gastrointestinal tract, spleen, pancreas, skin, fat, and hindlimb bones decreased during hypoxia; blood flow decreased in absolute values only in stomach and fat. Oxygen supply to brain, respiratory muscles, and liver increased during hypoxia, whereas it decreased in the remaining organs investigated.

Effect of water temperature on diuresis-natriuresis: AVP, ANP, and urodilatin during immersion in men

1994 ◽  
Vol 77 (4) ◽  
pp. 1919-1925 ◽  
Author(s):  
S. Nakamitsu ◽  
S. Sagawa ◽  
K. Miki ◽  
F. Wada ◽  
K. Nagaya ◽  
...  
Keyword(s):  
Water Temperature ◽  
Peripheral Resistance ◽  
Free Water ◽  
Plasma Renin ◽  
Urine Flow ◽  
Thoracic Impedance ◽  
Esophageal Temperature ◽  
Experimental Conditions ◽  
Free Water Clearance ◽  
Air Control

Effects of water temperature on diuresis, natriuresis, and associated endocrine responses during head-out immersion were studied in eight men (23.4 +/- 0.3 yr) during four 5-h experimental conditions: air control at 28 degrees C and immersion at 34.5 degrees C [thermoneutral (Tnt)], 36 degrees C [above Tnt (aTnt)], and 32 degrees C [below Tnt (bTnt)]. Esophageal temperature decreased by approximately 0.4 degrees C in bTnt and increased by approximately 0.5 degrees C in aTnt. Cardiac output increased by approximately 80% in aTnt and approximately 40% in bTnt while thoracic impedance, an index of central blood pooling, decreased by 7.5 omega in bTnt (NS vs. Tnt) and 8.8 omega in aTnt (P < 0.05 vs. Tnt and bTnt). Total peripheral resistance decreased at all temperatures (50% in aTnt, 20% in bTnt). Urine flow and Na+ excretion increased by sixfold in bTnt and Tnt but by only threefold in aTnt. Creatinine clearance was unchanged while osmolal clearance (but not free water clearance) increased two-fold with all immersions. Plasma atrial natriuretic peptide (ANP), urinary urodilatin, and urinary guanosine 3′,5′-cyclic monophosphate increased while plasma renin activity, aldosterone, and arginine vasopressin (AVP) decreased similarly at all temperatures. bTnt did not potentiate diuresis by selective attenuation of AVP. The overall natriuretic response exhibited a higher correlation with urodilatin (r = 0.45, P < 0.001) than with ANP (r = 0.26, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional circulatory responses to head-out water immersion in conscious dogs

1987 ◽  
Vol 253 (2) ◽  
pp. R254-R263 ◽  
Author(s):  
G. Hajduczok ◽  
K. Miki ◽  
J. R. Claybaugh ◽  
S. K. Hong ◽  
J. A. Krasney
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Water Immersion ◽  
Local Heating ◽  
Peripheral Resistance ◽  
Tissue Perfusion ◽  
Conscious Dogs ◽  
Metabolic Demand ◽  
Blood Flows ◽  
Total Brain

We determined the regional blood flow responses to head-out water immersion (WI) in intact (INT) and cardiac-denervated (CD) conscious dogs. Immersing dogs in thermoneutral water (37 degrees C) in the quadruped position for 100 min resulted in significant increases in cardiac output (Qco) above control values by 38.7% in the INT dogs and 39.2% in the CD dogs (P less than 0.01). Arterial pressure increased by 32 and 34.7% in the INT and CD groups, respectively, during WI, with no significant changes occurring in the calculated total peripheral resistance. Regional blood flow responses were measured with 15-microns radiolabeled microspheres. Flows in the INT and CD groups increased significantly to the heart (40, 38%), skin (93, 96%), fat (79, 83%), diaphragm (44, 48%), and intercostal muscles (58, 55%), whereas there were no changes in renal cortical blood flows during WI. Total brain blood flows did not change significantly on immersion; however, blood flows in both INT and CD animals were increased to the cerebellum (19, 22%), but a significant decrease in pituitary flow (52%) was observed only in the CD group during WI. Gastrointestinal tissue flows increased only during early WI in both INT (45%) and CD (47%) animals. However, blood flows to the skeletal muscles increased only during late WI in the INT (53%) and CD (47%) groups. There were no significant differences between the INT and CD groups. Rectal temperatures and systemic O2 consumption (VO2) were unchanged during WI in both groups of animals. These observations indicate that WI leads to a sustained elevation of Qco accompanied by selective increases in regional tissue perfusion that may be accounted for in some tissues by an increase in metabolic demand or by local heating responses and produces a time-dependent redistribution of blood flow away from the gastrointestinal tissues toward skeletal muscle tissues, which may be due to a partial uncoupling of the normal Q/VO2 relationship. This may be caused by thermal or central neurohumoral mechanisms. These regional circulatory responses are not dependent on the presence of the cardiac nerves.

Effect of Prolactin on Glomerular Filtration Rate

1978 ◽  
Vol 55 (4) ◽  
pp. 335-339 ◽  
Author(s):  
A. L. Riley ◽  
T. C. Hagen ◽  
J. E. Stefaniak
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Free Water ◽  
Flow Distribution ◽  
Fractional Excretion ◽  
Free Water Clearance ◽  
Fractional Excretion Of Sodium ◽  
Ovine Prolactin

1. The effect of infusion of ovine prolactin was studied in anaesthetized dogs pretreated with bromocryptine to reduce the release of endogenous prolactin. 2. Prolactin, injected intravenously and also directly into one kidney, resulted in a 12–18% increase in glomerular filtration rate (GFR) by both kidneys. 3. This increased GFR was not associated with any demonstrable changes in whole-kidney blood flow, distribution of intrarenal blood flow, fractional excretion of sodium or osmolar or free-water clearance. 4. We conclude that ovine prolactin produced an increase in GFR not dependent on an increase in whole-kidney plasma flow.

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