Protective role of NO in the regional hemodynamic changes during acute endotoxemia in rats

The role of NO during the first hour of endotoxemia is still controversial. To evaluate whether NO is protective or detrimental to the regulation of systemic blood pressure, cardiac output (CO), and organ perfusion in rats during acute endotoxemia, we have studied the effects of inhibition of NO synthesis. Thirty minutes after 0.1 mg NG-nitro-L-arginine (L-NNA; group L, n = 7, partial inhibition), 1 mg L-NNA (group H, n = 6, complete inhibition), or saline (group E, n = 7) intravenous infusion, anesthetized volume-loaded rats were infused with endotoxin Escherichia coli O127:B8 (8 mg.kg-1 x h-1) from time (t) = 0 to 60 min. Organ blood flow was measured with radioactive microspheres. In group H, at time 0, CO was lower than in group E (by -29%; P < 0.05), and systemic vascular resistance (SVR) was higher than in groups E and L (by 72 and 51%, respectively; P < 0.05). Perfusion of the pancreas, stomach, intestines, and kidney was lower (P < 0.05) and corresponding organ vascular resistance (OVR) higher (P < 0.05) in group H than in groups E and L (except kidney in group L). At t = 60 min, in groups H and L, CO was lower (by -45 and -26%, respectively; P < 0.05) and SVR was higher (by 112 and 54%, respectively; P < 0.05) than in group E. In group L only blood flow to the heart, pancreas, intestines, and kidney was significantly lower than in group E, and corresponding OVR was higher.(ABSTRACT TRUNCATED AT 250 WORDS)

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Characterization and cardiovascular actions of endothelin-1 and endothelin-3 from the American alligator

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00733.2000 ◽

2002 ◽

Vol 282 (2) ◽

pp. R594-R602 ◽

Cited By ~ 8

Author(s):

Björn Platzack ◽

Yuqi Wang ◽

Dane Crossley ◽

Valentine Lance ◽

James W. Hicks ◽

...

Keyword(s):

Blood Flow ◽

Vascular Resistance ◽

Biological Activities ◽

Systemic Blood Pressure ◽

Second Phase ◽

Systemic Blood ◽

Cardiovascular Actions ◽

Dose Dependent Decrease ◽

Alligator Mississipiensis ◽

Dose Dependent

The structures and biological activities of the isoforms of endothelin (ET) in a reptile are unknown. ET-3, whose primary structure is identical to human ET-3 except for the substitution Phe4 → Tyr, and a peptide identical to human ET-1 were isolated from an extract of the lung of the alligator, Alligator mississipiensis. Bolus intravenous injections of alligator ET-3 (10, 30, and 100 pmol/kg) into anesthetized alligators produced dose-dependent decreases in systemic blood pressure (Psys) and systemic vascular resistance (Rsys) without change in heart rate (HR), systemic blood flow (Qsys), pulmonary pressure (Ppul), pulmonary vascular resistance (Rpul), or pulmonary blood flow (Qpul). At a dose of 300 pmol/kg, the initial vasodilatation was followed by an increase in Rsys and decreases in Qsys and Ppul. The response to intravenous human/alligator ET-1 (10, 30, 100, and 300 pmol/kg) was biphasic at all doses with initial decreases in Psys and Rsys being followed by sustained increases in these parameters. In the pulmonary circulation, ET-1 produced a dose-dependent decrease in Qpul and an increase in Rpul during the first phase of the response but no significant change during the second phase. There was no change in HR in response to ET-1. The vasodilatator action of arginine, but not ET-1, was attenuated by N ω-nitro-l-arginine methyl ester, indicating that the effect of the peptide is probably not mediated through increased synthesis of nitric oxide. The data demonstrate that the structure of the ET isoforms has been strongly conserved during the evolution of vertebrates but that cardiovascular actions differ significantly between the alligator and mammals, especially in the magnitude and duration of the hypotensive response.

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Circulatory changes following premature delivery in a baboon model of hyaline membrane disease

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.261.4.h1148 ◽

1991 ◽

Vol 261 (4) ◽

pp. H1148-H1154 ◽

Cited By ~ 3

Author(s):

J. P. Kinsella ◽

D. R. Gerstmann ◽

R. A. Delemos

Keyword(s):

Blood Flow ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Oxygen Transport ◽

Ductus Arteriosus ◽

Hyaline Membrane Disease ◽

Premature Delivery ◽

Organ Blood Flow ◽

Hemodynamic Changes ◽

Hyaline Membrane

The premature baboon delivered by hysterotomy at 140 +/- 2 days (75%) gestation develops hyaline membrane disease (HMD) and left-to-right (L-R) shunting through the patent ductus arteriosus (PDA). To characterize hemodynamic changes that follow premature delivery, we measured systemic and organ blood flow, oxygen transport, and systemic vascular resistance over the first 96 h of life. We compared these measurements with those from more mature animals of the same species. Radiolabeled microspheres were used to measure organ blood flow (in ml.min-1.g-1) at 3 (n = 18), 23 (n = 17), and 96 h (n = 4) in the premature animals, and at 13 +/- 4 mo in the older animals (n = 5). Premature animals demonstrated over the first 96 h of life significant hemodynamic changes that included decreased systemic vascular resistance (P less than 0.001), increased systemic (P less than 0.05), intestinal (P less than 0.05), and hepatic blood flow (P less than 0.05), as well as resolution of L-R PDA shunting. These 96-h values were similar to those of the more mature infant baboons. Blood flow and oxygen transport to the kidneys and cerebrum did not significantly increase over the first 96 h in premature baboons and were significantly less than those of 13-mo-old animals (P less than 0.01, both). We speculate that low renal and cerebral blood flow in the 140-day premature baboon are manifestations of multisystem immaturity and, as such, may represent persistent physiological disturbances that are distinct from the severity of underlying lung disease in HMD.

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Lack of effect of a single oral dose of cyclosporine on systemic blood pressure and on forearm blood flow and vascular resistance in humans☆

American Journal of Hypertension ◽

10.1016/s0895-7061(98)00156-3 ◽

1998 ◽

Vol 11 (11) ◽

pp. 1371-1375 ◽

Cited By ~ 1

Author(s):

J GALVAODELIMA ◽

F CONSOLIMCOLOMBO ◽

H FERREIRALOPES ◽

G GUERRARICCIO ◽

E KRIEGER

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Oral Dose ◽

Single Oral Dose ◽

Vascular Resistance ◽

Forearm Blood Flow ◽

Systemic Blood Pressure ◽

Systemic Blood

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Effects of artificial bleeding upon the systemic blood pressure and the blood flow of the internal carotid artery and the role of the sinus nerve in rabbits

Journal of Nippon Medical School ◽

10.1272/jnms1923.45.181 ◽

1978 ◽

Vol 45 (3) ◽

pp. 181-186

Author(s):

Masanori Ikeda

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Carotid Artery ◽

Internal Carotid Artery ◽

Internal Carotid ◽

Systemic Blood Pressure ◽

Systemic Blood

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Renal effect of meclofenamate in presence and absence of superfusion bioassay

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.3.711 ◽

1976 ◽

Vol 230 (3) ◽

pp. 711-714 ◽

Cited By ~ 10

Author(s):

S Satoh ◽

BG Zimmerman

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Renal Artery ◽

Renal Blood Flow ◽

Vascular Resistance ◽

Systemic Blood Pressure ◽

Prostaglandin E ◽

Renal Effect ◽

Systemic Blood ◽

Renal Vascular

Systemic blood pressure (SBP), renal blood flow (RBF), renal vascular resistance (RVR), and arterial and renal venous prostaglandin E (PGE) concentrations were determined in pentobarbital-anesthetized dogs.The effect of sodium meclofenamate infused into the renal artery was compared under two sets of conditions. In experiments carried out under control conditions, SBP, RBF, and RVR were stable and meclofenamate caused only a slight decrease in RBF (5.4%) and increase in RVR.

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Mesenteric Hemodynamics During Hemorrhagic Shock in the Dog With Functional Absence of the Liver

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.193.3.599 ◽

1958 ◽

Vol 193 (3) ◽

pp. 599-604 ◽

Cited By ~ 11

Author(s):

Ewald E. Selkurt

Keyword(s):

Blood Flow ◽

Hemorrhagic Shock ◽

Cardiovascular System ◽

General Circulation ◽

Protective Role ◽

Hemodynamic Changes ◽

Vascular Bed ◽

Gain Access ◽

Hyperemic Response

The sequence of hemorrhagic shock was studied in dogs with functional absence of the liver produced by ligation of vascular inflow circuits. Establishment of a portal to jugular shunt permitted continual measurement of intestinal blood flow. It was found that this vascular bed exhibited the characteristic hyperemic response previously observed in dogs with intact livers, studied under similar conditions. Other hemodynamic changes symptomatic of irreversibility were observed. It is concluded that the liver made anoxic during shock does not contribute to irreversibility, and that it is more likely that it exerts a protective role. An hypothesis is advocated that hypotension creates conditions in the intestinal bed which favor production or release of vasodepressor agents or material toxic to the cardiovascular system. In the absence, or impairment of the normal protective role of the liver, these gain access into the general circulation with deleterious consequences to circulatory homeostasis.

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Methylprednisolone on circulating eicosanoids and vasomotor tone after endotoxin

Journal of Applied Physiology ◽

10.1152/jappl.1986.61.1.185 ◽

1986 ◽

Vol 61 (1) ◽

pp. 185-191 ◽

Cited By ~ 11

Author(s):

C. A. Hales ◽

R. D. Brandstetter ◽

C. F. Neely ◽

M. B. Peterson ◽

D. Kong ◽

...

Keyword(s):

Blood Pressure ◽

Vascular Resistance ◽

Systemic Blood Pressure ◽

Physiological Effect ◽

High Dose ◽

Systemic Blood ◽

Eicosanoid Production ◽

Circulating Levels

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin. The stable metabolites of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay. Methylprednisolone by itself did not alter circulating eicosanoids but when given 2.5 h before endotoxin not only failed to inhibit endotoxin-induced eicosanoid production but actually resulted in higher circulating levels of 6-keto-PGF1 alpha (P less than 0.05) compared with animals receiving endotoxin alone. Indomethacin prevented the steroid-enhanced concentrations of 6-keto-PGF1 alpha after endotoxin and prevented the greater fall (P less than 0.05) in systemic blood pressure and systemic vascular resistance with steroid plus endotoxin than occurred with endotoxin alone. Administration of methylprednisolone immediately before endotoxin resulted in enhanced levels (P less than 0.05) of both TxB2 and 6-keto-PGF1 alpha but with a fall in systemic blood pressure and vascular resistance similar to the animals pretreated by 2.5 h. In contrast to the early steroid group in which all of the hypotensive effect was due to eicosanoids, in the latter group steroids had an additional nonspecific effect. Thus, in vivo, high-dose steroids did not prevent endotoxin-induced increases in eicosanoids but actually increased circulating levels of TxB2 and 6-keto-PGF1 alpha with a physiological effect favoring vasodilation.

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Control of Blood Pressure and the Distribution of Blood Flow

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462300012551 ◽

1991 ◽

Vol 7 (S1) ◽

pp. 79-84 ◽

Cited By ~ 1

Author(s):

Hans T. Versmold

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Cardiac Output ◽

Peripheral Resistance ◽

Systemic Blood Pressure ◽

Adrenergic Innervation ◽

Systemic Blood ◽

Low Cardiac Output ◽

Neurohumoral Control ◽

The Brain

Systemic blood pressure (BP) is the product of cardiac output and total peripheral resistance. Cardiac output is controlled by the heart rate, myocardial contractility, preload, and afterload. Vascular resistance (vascular hindrance × viscosity) is under local autoregulation and general neurohumoral control through sympathetic adrenergic innervation and circulating catecholamines. Sympathetic innovation predominates in organs receivingflowin excess of their metabolic demands (skin, splanchnic organs, kidney), while innervation is poor and autoregulation predominates in the brain and heart. The distribution of blood flow depends on the relative resistances of the organ circulations. During stress (hypoxia, low cardiac output), a raise in adrenergic tone and in circulating catecholamines leads to preferential vasoconstriction in highly innervated organs, so that blood flow is directed to the brain and heart. Catecholamines also control the levels of the vasoconstrictors renin, angiotensin II, and vasopressin. These general principles also apply to the neonate.

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Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases

AJP Renal Physiology ◽

10.1152/ajprenal.00124.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. F1324-F1332 ◽

Cited By ~ 82

Author(s):

Manish M. Tiwari ◽

Robert W. Brock ◽

Judit K. Megyesi ◽

Gur P. Kaushal ◽

Philip R. Mayeux

Keyword(s):

Nitric Oxide ◽

Renal Failure ◽

Blood Flow ◽

Saline Group ◽

No Production ◽

Capillary Perfusion ◽

Peritubular Capillary ◽

Synthase Inhibitor ◽

Peritubular Capillary Perfusion

Acute renal failure (ARF) is a frequent and serious complication of endotoxemia caused by lipopolysaccharide (LPS) and contributes significantly to mortality. The present studies were undertaken to examine the roles of nitric oxide (NO) and caspase activation on renal peritubular blood flow and apoptosis in a murine model of LPS-induced ARF. Male C57BL/6 mice treated with LPS ( Escherichia coli) at a dose of 10 mg/kg developed ARF at 18 h. Renal failure was associated with a significant decrease in peritubular capillary perfusion. Vessels with no flow increased from 7 ± 3% in the saline group to 30 ± 4% in the LPS group ( P < 0.01). Both the inducible NO synthase inhibitor l- N6-1-iminoethyl-lysine (l-NIL) and the nonselective caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD) prevented renal failure and reversed perfusion deficits. Renal failure was also associated with an increase in renal caspase-3 activity and an increase in renal apoptosis. Both l-NIL and Z-VAD prevented these changes. LPS caused an increase in NO production that was blocked by l-NIL but not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal caspases and the resulting disruption in peritubular blood flow are an important mechanism of LPS-induced ARF.

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