At
            2
            Receptor-Mediated Vasodilation in the Heart: Effect of Myocardial Infarction.

P64 To investigate the functional consequences of the changes in AT 2 receptor density that have been reported following myocardial infarction (MI; Matsubara, Circ Res, 1998), three consecutive 10 min intravenous infusions of angiotensin (Ang) II (100, 300 and 1000 ng/kg/min) were given to 19 sham-operated and 16 coronary artery-ligated rats, at four weeks after surgery, pretreated with either saline, the AT 1 receptor antagonist irbesartan (100 μg/kg/min for 30 min), or the AT 2 receptor antagonist PD123319 (20 μg/kg/min for 30 min, followed by continuous infusion). Systemic and regional hemodynamic effects were studied using the radioactive microsphere method. Ang II induced comparable changes in sham and MI rats in mean arterial pressure (MAP; maximally +30±10% and +30±8%, resp., mean±SEM) and systemic vascular conductance (cardiac output/MAP, -27±8% and -32±5%, resp.). Cardiac output decreased in MI (-20±5%) but not in sham rats. Irbesartan decreased MAP by 34% (sham) and 22% (MI), increased SVC by 41% (sham) and 24% (MI), and blocked the Ang II-mediated systemic hemodynamic effects in both sham and MI rats, while PD123319 did not affect these parameters. Myocardial conductance at baseline was diminished in MI vs. sham rats (41±3 vs. 55±6 μl/min/mmHg, resp.), while renal conductance was comparable in both groups (168±9 vs. 156±18 μl/min/mmHg, resp.). Ang II increased myocardial conductance maximally to 56±3 (MI) and 72±3 (sham) μl/min/mmHg, and decreased renal conductance to 67±4 (MI) and 74±8 (sham) μl/min/mmHg. Irbesartan increased renal, but not myocardial, conductance in both groups and blocked the Ang II-mediated renal vasoconstriction. PD123319 did not affect renal or myocardial conductance and blocked the Ang II-mediated myocardial vasodilation in sham but not in MI rats. PD123319 did not affect the Ang II-mediated renal responses. In conclusion, Ang II increases myocardial, but not renal, conductance (i.e., induces vasodilation) via AT 2 receptor stimulation. The inability of PD123319 to block this response in MI rats suggests either an upregulation of AT 2 receptors or a role for non-AT 1 , non-AT 2 receptors in the infarcted heart.

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MIC-II — A program for the determination of cardiac output, arterio-venous shunt and regional blood flow using the radioactive microsphere method

Computer Programs in Biomedicine ◽

10.1016/0010-468x(79)90014-x ◽

1979 ◽

Vol 9 (1) ◽

pp. 19-38 ◽

Cited By ~ 94

Author(s):

R. Schosser ◽

K.-E. Arfors ◽

K. Messmer

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Regional Blood Flow ◽

Radioactive Microsphere ◽

Venous Shunt ◽

Microsphere Method ◽

Radioactive Microsphere Method

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AT2 receptor-mediated vasodilation in the heart: effect of myocardial infarction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.6.h2590 ◽

2001 ◽

Vol 281 (6) ◽

pp. H2590-H2596 ◽

Cited By ~ 24

Author(s):

Martin P. Schuijt ◽

Munesh Basdew ◽

Richard van Veghel ◽

René de Vries ◽

Pramod R. Saxena ◽

...

Keyword(s):

Receptor Antagonist ◽

Coronary Artery Ligation ◽

Sham Operation ◽

Ang Ii ◽

Artery Ligation ◽

Systemic Hemodynamic ◽

Functional Consequences ◽

Receptor Upregulation ◽

Renal Vascular

To investigate the functional consequences of postinfarct cardiac angiotensin (ANG) type 2 (AT2) receptor upregulation, rats underwent coronary artery ligation or sham operation and were infused with ANG II 3–4 wk later, when scar formation is complete. ANG II increased mean arterial pressure (MAP) more modestly in infarcted animals than in sham animals. The AT1 receptor antagonist irbesartan, but not the AT2 receptor antagonist PD123319, decreased MAP and antagonized the ANG II-mediated systemic hemodynamic effects. Myocardial (MVC) but not renal vascular conductance (RVC) was diminished in infarcted versus sham rats. ANG II did not affect MVC and reduced RVC in all rats. MVC was unaffected by irbesartan and PD123319 in all animals. However, with PD123319, ANG II reduced MVC in sham but not infarcted animals, and, with irbesartan, ANG II increased MVC in infarcted but not sham animals. Irbesartan increased RVC and antagonized the ANG II-mediated renal effects in all animals. RVC, at baseline or with ANG II, was not affected by PD123319 in infarcted and sham animals. In conclusion, coronary but not renal AT2 receptor stimulation results in vasodilation, and this effect is enhanced in infarcted rats.

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Hemodynimic effects of systemic and central administration of clonidine in the monkey

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1975.228.4.1276 ◽

1975 ◽

Vol 228 (4) ◽

pp. 1276-1279 ◽

Cited By ~ 8

Author(s):

P Bolme ◽

RP Forsyth ◽

T Ishizaki ◽

KL Melmon

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Regional Blood Flow ◽

Systemic Arterial Pressure ◽

Intraventricular Injection ◽

Central Administration ◽

New Information ◽

Before And After ◽

Microsphere Method ◽

Radioactive Microsphere Method

Systemic and regional hemodynamic changes were measured in restrained, conscious rhesus monkeys with indwelling arterial and venous catheters before and after clonidine (5 and 15 mug/kg) was slowly infused intravenously or smaller doses (2 mug/kg) were injected into a lateral cerebral ventricle. Dye-dilution cardiac outputs and the complete distribution of cardiac output were obtained intermittently with the use of the radioactive microsphere method. After the higher intravenous dose and the intraventricular injection, systemic arterial pressure was significantly lowered for 30-45 min. Both of these groups had similar changes in the redistribution of cardiac output and blood flow that outlasted the hypotensive period. Blood flow was maintained or increased in the hepatic and renal arteries at the expense of skin; flow to skeletal muscle and brain also decreased during the first hour. These data support previous studies that indicate that the primary action of clonidine is in the central nervous system and, in addition, add new information about the regional blood flow changes evoked by clonidine.

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Validity Studies of the Radioactive Microsphere Method for the Study of the Distribution of Cardiac Output, Organ Blood Flow, and Resistance in the Conscious Rhesus Monkey

Cardiovascular Research ◽

10.1093/cvr/3.4.426 ◽

1969 ◽

Vol 3 (4) ◽

pp. 426-432 ◽

Cited By ~ 102

Author(s):

B. I. Hoffbrand ◽

R. P. Forsyth

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Rhesus Monkey ◽

Organ Blood Flow ◽

Radioactive Microsphere ◽

Microsphere Method ◽

Radioactive Microsphere Method ◽

Validity Studies ◽

Distribution Of Cardiac Output

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A Simple Radioactive Microsphere Method for Measuring Regional Flow and Cardiac Output

Investigative Radiology ◽

10.1097/00004424-197405000-00002 ◽

1974 ◽

Vol 9 (3) ◽

pp. 126-132 ◽

Cited By ~ 84

Author(s):

Royal J. Bartrum ◽

Daniel M. Berkowitz ◽

Norman K. Hollenberg

Keyword(s):

Cardiac Output ◽

Regional Flow ◽

Radioactive Microsphere ◽

Microsphere Method ◽

Radioactive Microsphere Method

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Comparison of the Fick principle and the radioactive microsphere method in measuring cardiac output during haemorrhagic shock

Acta Physiologica Scandinavica ◽

10.1111/j.1748-1716.1985.tb07590.x ◽

1985 ◽

Vol 123 (3) ◽

pp. 293-297 ◽

Cited By ~ 3

Author(s):

C. LUNDBERG ◽

M. H. SCHOENBERG

Keyword(s):

Cardiac Output ◽

Haemorrhagic Shock ◽

Fick Principle ◽

Radioactive Microsphere ◽

Microsphere Method ◽

Radioactive Microsphere Method

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Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1983.244.4.h628 ◽

1983 ◽

Vol 244 (4) ◽

pp. H628-H633 ◽

Cited By ~ 1

Author(s):

M. A. Pfeffer ◽

J. M. Pfeffer ◽

R. A. Lewis ◽

E. Braunwald ◽

E. J. Corey ◽

...

Keyword(s):

Cardiac Output ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Total Peripheral Resistance ◽

Peripheral Resistance ◽

Right Atrial ◽

Moderate Pressure ◽

Hemodynamic Effects ◽

Systemic Hemodynamic ◽

Leukotriene D4

Although local administration of the sulfidopeptide leukotrienes into cutaneous and coronary vascular beds indicates that these naturally occurring metabolites of arachidonic acid are vasoconstrictors, their systemic administration has produced both pressor and depressor responses. The systemic hemodynamic effects of intravenous leukotriene C4 (LTC4) and leukotriene D4 (LTD4) were assessed in ether-anesthetized rats and compared with the effects produced by equimolar doses (2 X 10(-10) to 4 X 10(-8) mol/kg) of norepinephrine and angiotensin. Mean arterial pressure, right atrial pressure, and cardiac output (electromagnetic flowmetry) were recorded during bolus administrations of these vasoactive compounds. LTC4 and LTD4 had similar hemodynamic effects that were characterized by moderate pressure elevations produced by dose-dependent increases in total peripheral resistance, since cardiac output declined. Although the peak mean arterial pressure levels produced by LTC4 and LTD4 (135 +/- 7 and 129 +/- 5 mmHg, respectively) were less than those by norepinephrine (157 +/- 3 mmHg) and angiotensin (174 +/- 5 mmHg), the peak total peripheral resistance values of LTC4 and LTD4 (2.23 +/- 0.32 and 1.86 +/- 0.17 mmHg X ml-1 X min-1, respectively) were between those of the well-known vasopressors, norepinephrine (1.50 +/- 0.09) and angiotensin (2.72 +/- 0.41). The pressor response to LTC4 and LTD4 was less marked than that to norepinephrine and to angiotensin because of the concomitant reduction in cardiac output. These results indicate that LTC4 and LTD4 are systemic vasoconstrictors with potencies similar to those of norepinephrine and angiotensin.

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Systemic hemodynamic effects of endothelin in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.258.3.h787 ◽

1990 ◽

Vol 258 (3) ◽

pp. H787-H792 ◽

Cited By ~ 6

Author(s):

A. J. King ◽

J. M. Pfeffer ◽

M. A. Pfeffer ◽

B. M. Brenner

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Early Phase ◽

Late Phase ◽

Peripheral Resistance ◽

Resistance Index ◽

Right Atrial ◽

Ang Ii ◽

Hemodynamic Effects ◽

Systemic Hemodynamic

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.

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