Rho kinase and Ca2+ entry mediate increased pulmonary and systemic vascular resistance in l-NAME-treated rats

2007 ◽  
Vol 293 (5) ◽  
pp. L1306-L1313 ◽  
Author(s):  
Jasdeep S. Dhaliwal ◽  
David B. Casey ◽  
Anthony J. Greco ◽  
Adeleke M. Badejo ◽  
Thomas B. Gallen ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Rho Kinase ◽  
Systemic Arterial Pressure ◽  
Intravenous Injections ◽  
Pulmonary Arterial ◽  
Dose Dependent

The small GTP-binding protein and its downstream effector Rho kinase play an important role in the regulation of vasoconstrictor tone. Rho kinase activation maintains increased pulmonary vascular tone and mediates the vasoconstrictor response to nitric oxide (NO) synthesis inhibition in chronically hypoxic rats and in the ovine fetal lung. However, the role of Rho kinase in mediating pulmonary vasoconstriction after NO synthesis inhibition has not been examined in the intact rat. To address this question, cardiovascular responses to the Rho kinase inhibitor fasudil were studied at baseline and after administration of an NO synthesis inhibitor. In the intact rat, intravenous injections of fasudil cause dose-dependent decreases in systemic arterial pressure, small decreases in pulmonary arterial pressure, and increases in cardiac output. l-NAME caused a significant increase in pulmonary and systemic arterial pressures and a decrease in cardiac output. The intravenous injections of fasudil after l-NAME caused dose-dependent decreases in pulmonary and systemic arterial pressure and increases in cardiac output, and the percent decreases in pulmonary arterial pressure in response to the lower doses of fasudil were greater than decreases in systemic arterial pressure. The Ca++ entry blocker isradipine also decreased pulmonary and systemic arterial pressure in l-NAME-treated rats. Infusion of sodium nitroprusside restored pulmonary arterial pressure to baseline values after administration of l-NAME. These data provide evidence in support of the hypothesis that increases in pulmonary and systemic vascular resistance following l-NAME treatment are mediated by Rho kinase and Ca++ entry through L-type channels, and that responses to l-NAME can be reversed by an NO donor.

Cardiorespiratory Disturbances Associated with Infective Fever in Man: Studies of Ethiopian Louse-Borne Relapsing Fever

1970 ◽  
Vol 39 (1) ◽  
pp. 123-145 ◽  
Author(s):  
D. A. Warrell ◽  
Helen M. Pope ◽  
E. H. O. Parry ◽  
P. L. Perine ◽  
A.D.M. Bryceson
Keyword(s):  
Cardiac Output ◽  
Body Temperature ◽  
Arterial Pressure ◽  
Metabolic Rate ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Ventilation ◽  
Systemic Arterial Pressure ◽  
Relapsing Fever ◽  
Pulmonary Arterial

1. Nineteen patients with louse-borne relapsing fever were studied in Addis Abeba (altitude 2285 m). 2. Following treatment with tetracycline a febrile Jarisch—Herxheimer-like reaction developed which showed the phases described in artificially-induced endotoxin fever. 3. During the chill phase body temperature, metabolic rate and pulmonary ventilation increased. Despite alveolar hyperventilation pulmonary venous admixture was high. Cardiac output, heart rate and systemic arterial pressure increased but pulmonary arterial pressure decreased. 4. During the flush phase systemic arterial pressure fell and remained low for many hours due to reduced vascular resistance, but pulmonary arterial pressure and inflow resistance increased. Small increases in glucose, lactate, and pyruvate concentrations were prevented by inhaling oxygen. 5. Stimulation of metabolic rate, ventilation and cardiac output during the reaction was not due simply to increased body temperature, hypoxia, or acidosis but was probably attributable to spirochaetal endotoxin. 6. Limitation of pulmonary oxygen diffusion may have been responsible for the impaired pulmonary oxygen uptake in these patients. 7. During the prolonged flush phase a greatly increased cardiac output is necessary to maintain systemic arterial pressure because of the very low vascular resistance. Prevention of extracellular fluid volume depletion, early detection and prompt treatment of cardiac failure and oxygen therapy may reduce fatalities during this critical period but hydrocortisone in large doses failed to reduce the severity of the reaction.

Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins

1983 ◽  
Vol 55 (2) ◽  
pp. 558-561 ◽  
Author(s):  
J. Lindenfeld ◽  
J. T. Reeves ◽  
L. D. Horwitz
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Cyclooxygenase Inhibitors ◽  
Pulmonary Resistance ◽  
Before And After ◽  
Pulmonary Arterial

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.

Effects of arteriovenous fistula on systemic and pulmonary circulations

1964 ◽  
Vol 207 (6) ◽  
pp. 1319-1324 ◽  
Author(s):  
Jiro Nakano ◽  
Christian De Schryver
Keyword(s):  
Cardiac Output ◽  
Blood Transfusion ◽  
Arterial Pressure ◽  
Left Atrial ◽  
Pulmonary Arterial Pressure ◽  
Peripheral Resistance ◽  
Systemic Arterial Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Pulmonary Arterial

The effects of arteriovenous fistulas of different magnitudes on cardiovascular dynamics were studied in anesthetized dogs. It was found that A-V fistula decreases mean systemic arterial pressure, effective systemic blood flow, total and pulmonary peripheral resistances, whereas it increases heart rate, total cardiac output, stroke volume, left atrial pressure, pulmonary arterial pressure, and systemic peripheral resistance. The magnitude of the above hemodynamic changes was essentially proportional to the size of the fistula. At equivalent increments in total cardiac output produced by A-V fistula and blood transfusion, the former condition causes a greater increase in pulmonary arterial pressure than the latter, although both conditions decrease the pulmonary peripheral resistance by the same degree. It was also found that, at equivalent left atrial pressures, left ventricular stroke work with A-V fistula was greater than that with blood transfusion.

Hemodynamic effects of arginine vasopressin in rats adapted to chronic hypoxia

1989 ◽  
Vol 66 (1) ◽  
pp. 151-160 ◽  
Author(s):  
H. K. Jin ◽  
R. H. Yang ◽  
Y. F. Chen ◽  
R. M. Thornton ◽  
R. M. Jackson ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Arginine Vasopressin ◽  
Pulmonary Arterial Pressure ◽  
Systemic Arterial Pressure ◽  
Systemic Hemodynamic ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
Air Control

Acute and chronic pulmonary and systemic hemodynamic responses to arginine vasopressin (AVP) were examined in 4-wk hypoxia-adapted and air control rats. AVP, administered intravenously as bolus injections or sustained infusions, produced major dose-dependent V1-receptor-mediated reductions in mean pulmonary arterial pressure in hypoxia-adapted rats. These effects were comparable in pentobarbital-anesthetized, thoracotomized animals and in conscious, intact rats. Chronic infusions of AVP induced a sustained reduction in mean pulmonary arterial pressure and partially prevented the development of pulmonary hypertension without changing systemic arterial pressure. AVP induced significant decreases in cardiac output in both groups; the cardiac output response was not significantly different in hypoxia-adapted and air control animals. AVP induced almost no change in MPAP in air control rats. Furthermore the systemic pressor effects of AVP were significantly blunted in hypoxia-adapted rats compared with air controls. We conclude that the pulmonary depressor and blunted systemic pressor effects of AVP observed in hypoxia-adapted rats may be related to release of a vasodilator, such as endothelium-derived relaxing factor, vasodilator prostaglandins, or atrial natriuretic peptides. Further study is needed to elucidate these mechanisms and assess the usefulness of AVP and/or its analogues in the treatment and prevention of hypoxia-induced pulmonary hypertension.

scholarly journals Analysis of cardiovascular responses to the H2S donors Na2S and NaHS in the rat

2015 ◽  
Vol 309 (4) ◽  
pp. H605-H614 ◽  
Author(s):  
Daniel Yoo ◽  
Ryan C. Jupiter ◽  
Edward A. Pankey ◽  
Vishwaradh G. Reddy ◽  
Justin A. Edward ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Potassium Channels ◽  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Vascular Tissue ◽  
Sinus Node ◽  
Cardiovascular Responses ◽  
Systemic Arterial Pressure

Hydrogen sulfide (H2S) is an endogenous gaseous molecule formed from L-cysteine in vascular tissue. In the present study, cardiovascular responses to the H2S donors Na2S and NaHS were investigated in the anesthetized rat. The intravenous injections of Na2S and NaHS 0.03–0.5 mg/kg produced dose-related decreases in systemic arterial pressure and heart rate, and at higher doses decreases in cardiac output, pulmonary arterial pressure, and systemic vascular resistance. H2S infusion studies show that decreases in systemic arterial pressure, heart rate, cardiac output, and systemic vascular resistance are well-maintained, and responses to Na2S are reversible. Decreases in heart rate were not blocked by atropine, suggesting that the bradycardia was independent of parasympathetic activation and was mediated by an effect on the sinus node. The decreases in systemic arterial pressure were not attenuated by hexamethonium, glybenclamide, Nw-nitro-l-arginine methyl ester hydrochloride, sodium meclofenamate, ODQ, miconazole, 5-hydroxydecanoate, or tetraethylammonium, suggesting that ATP-sensitive potassium channels, nitric oxide, arachidonic acid metabolites, cyclic GMP, p450 epoxygenase metabolites, or large conductance calcium-activated potassium channels are not involved in mediating hypotensive responses to the H2S donors in the rat and that responses are not centrally mediated. The present data indicate that decreases in systemic arterial pressure in response to the H2S donors can be mediated by decreases in vascular resistance and cardiac output and that the donors have an effect on the sinus node independent of the parasympathetic system. The present data indicate that the mechanism of the peripherally mediated hypotensive response to the H2S donors is uncertain in the intact rat.

Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat

2008 ◽  
Vol 295 (5) ◽  
pp. L828-L836 ◽  
Author(s):  
Adeleke M. Badejo ◽  
Jasdeep S. Dhaliwal ◽  
David B. Casey ◽  
Thomas B. Gallen ◽  
Anthony J. Greco ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Systemic Arterial Pressure ◽  
Prior Exposure ◽  
Intravenous Injections ◽  
Pulmonary Vasodilator

The small GTP-binding protein Rho and its downstream effector, Rho-kinase, are important regulators of vasoconstrictor tone. Rho-kinase is upregulated in experimental models of pulmonary hypertension, and Rho-kinase inhibitors decrease pulmonary arterial pressure in rodents with monocrotaline and chronic hypoxia-induced pulmonary hypertension. However, less is known about responses to fasudil when pulmonary vascular resistance is elevated on an acute basis by vasoconstrictor agents and ventilatory hypoxia. In the present study, intravenous injections of fasudil reversed pulmonary hypertensive responses to intravenous infusion of the thromboxane receptor agonist, U-46619 and ventilation with a 10% O2 gas mixture and inhibited pulmonary vasoconstrictor responses to intravenous injections of angiotensin II, BAY K 8644, and U-46619 without prior exposure to agonists, which can upregulate Rho-kinase activity. The calcium channel blocker isradipine and fasudil had similar effects and in small doses had additive effects in blunting vasoconstrictor responses, suggesting parallel and series mechanisms in the lung. When pulmonary vascular resistance was increased with U-46619, fasudil produced similar decreases in pulmonary and systemic arterial pressure, whereas isradipine produced greater decreases in systemic arterial pressure. The hypoxic pressor response was enhanced by 5–10 mg/kg iv nitro-l-arginine methyl ester (l-NAME), and fasudil or isradipine reversed the pulmonary hypertensive response to hypoxia in control and in l-NAME-treated animals, suggesting that the response is mediated by Rho-kinase and L-type Ca2+ channels. These results suggest that Rho-kinase is constitutively active in regulating baseline tone and vasoconstrictor responses in the lung under physiological conditions and that Rho-kinase inhibition attenuates pulmonary vasoconstrictor responses to agents that act by different mechanisms without prior exposure to the agonist.

Adrenoceptor function in the bovine pulmonary circulation

1986 ◽  
Vol 64 (6) ◽  
pp. 689-693 ◽  
Author(s):  
Kevin J. Greenlees ◽  
Robert Gamble ◽  
Peter Eyre
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Pulmonary Arteries ◽  
Systemic Arterial Pressure ◽  
Venous Circulation ◽  
Arterial Ph ◽  
Pulmonary Arterial ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Arteries And Veins

The bovine pulmonary vascular response to α- and β-agonists was studied using an awake intact calf model. Pulmonary arterial pressure, pulmonary arterial wedge pressure, left atrial pressure, systemic arterial pressure, and cardiac output were measured in response to 3 min infusions of isoproterenol (β-agonist; 0.12, 0.24, 0.48, 0.9, and 1.8 μg∙kg−1∙min−1) and phenylephrine (α-agonist, 0.15, 0.30, 0.60, 1.15, and 2.30 μg∙kg−1∙min−1). Phenylephrine caused an increase in vascular resistance in the pulmonary arterial and venous compartments. The slope of the resistance in response to phenylephrine was greater in the pulmonary arterial than pulmonary venous circulation. Isoproterenol resulted in a dose-dependent decrease in vascular resistance in the pulmonary arteries and veins. The vascular resistance was decreased to the same level in the pulmonary arteries and veins although the arteries showed a greater percent change. In addition, isoproterenol infusion resulted in a transient decrease in arterial pH and increase in values for packed cell volume and haemoglobin.

scholarly journals Analysis of responses to the Rho-kinase inhibitor Y-27632 in the pulmonary and systemic vascular bed of the rat

2010 ◽  
Vol 299 (1) ◽  
pp. H184-H192 ◽  
Author(s):  
David B. Casey ◽  
Adeleke M. Badejo ◽  
Jasdeep S. Dhaliwal ◽  
James L. Sikora ◽  
Alex Fokin ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Guanylate Cyclase ◽  
Kinase Inhibitor ◽  
Pulmonary Arterial Pressure ◽  
Rho Kinase ◽  
Hypoxic Exposure ◽  
Intravenous Injections ◽  
Vasoconstrictor Response ◽  
Rho Kinase Inhibitor ◽  
Pulmonary Arterial

Responses to the Rho kinase inhibitor Y-27632 were investigated in the anesthetized rat. Under baseline conditions intravenous injections of Y-27632 decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressures were enhanced when baseline tone was increased with U-46619, and under elevated tone conditions Y-27632 produced similar percent decreases in pulmonary and systemic arterial pressures. Injections of Y-27632 prevented and reversed the hypoxic pulmonary vasoconstrictor response. The increase in pulmonary arterial pressure in response to ventilation with a 10% O2-90% N2 gas mixture was not well maintained during the period of hypoxic exposure. Treatment with the nitric oxide (NO) synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) increased pulmonary arterial pressure and prevented the decline or fade in the hypoxic pulmonary vasoconstrictor response. The hypoxic pulmonary vasoconstrictor response was reversed by Y-27632 in control and in l-NAME-treated animals. The Rho kinase inhibitor attenuated increases in pulmonary arterial pressures in response to intravenous injections of serotonin, angiotensin II, and Bay K 8644. Y-27632, sodium nitrite, and BAY 41-8543, a guanylate cyclase stimulator, decreased pulmonary and systemic arterial pressures and vascular resistances in monocrotaline-treated rats. These data suggest that Rho kinase is involved in the regulation of baseline tone and in the mediation of pulmonary vasoconstrictor responses. The present data suggest that the hypoxic pulmonary vasoconstrictor response is modulated by the release of NO that mediates the nonsustained component of the response in the anesthetized rat. These data suggest that Rho kinase and NOS play important roles in the regulation of vasoconstrictor tone in physiological and pathophysiological states and that monocrotaline-induced pulmonary hypertension can be reversed by agents that inhibit Rho kinase, generate NO, or stimulate soluble guanylate cyclase.

scholarly journals Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase stimulator, BAY 41-8543, are modulated by nitric oxide

2010 ◽  
Vol 299 (4) ◽  
pp. H1153-H1159 ◽  
Author(s):  
Adeleke M. Badejo ◽  
Vaughn E. Nossaman ◽  
Edward A. Pankey ◽  
Manish Bhartiya ◽  
Chandrika B. Kannadka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Guanylyl Cyclase ◽  
Pulmonary Arterial Pressure ◽  
Soluble Guanylyl Cyclase ◽  
Systemic Arterial Pressure ◽  
Intravenous Injections ◽  
Vasodilator Activity ◽  
Pulmonary Arterial ◽  
Vascular Beds

BAY 41-8543 is a nitric oxide (NO)-independent stimulator of soluble guanylyl cyclase (sGC). Responses to intravenous injections of BAY 41-8543 were investigated under baseline and elevated tone conditions and when NO synthase (NOS) was inhibited with Nω-nitro-l-arginine methyl ester (l-NAME). Under baseline conditions, intravenous injections of BAY 41-8543 caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and increases in cardiac output. When pulmonary arterial pressure was increased to ∼30 mmHg with an intravenous infusion of U-46619, intravenous injections of BAY 41-8543 produced larger dose-dependent decreases in pulmonary arterial pressure, and the relative decreases in pulmonary and systemic arterial pressure in response to the sGC stimulator were similar. Treatment with l-NAME markedly decreased responses to BAY 41-8543 when pulmonary arterial pressure was increased to similar values (∼30 mmHg) in U-46619-infused and in U-46619-infused plus l-NAME-treated animals. The intravenous injection of a small dose of sodium nitroprusside (SNP) when combined with BAY 41-8543 enhanced pulmonary and systemic vasodilator responses to the sGC stimulator in l-NAME-treated animals. The present results indicate that BAY 41-8543 has similar vasodilator activity in the systemic and pulmonary vascular beds when pulmonary vasoconstrictor tone is increased with U-46619. These results demonstrate that pulmonary and systemic vasodilator responses to BAY 41-8543 are significantly attenuated when NOS is inhibited by l-NAME and show that vasodilator responses to BAY 41-8543 are enhanced when combined with a small dose of SNP in l-NAME-treated animals. The present results are consistent with the concept that pulmonary and systemic vasodilator responses to the sGC stimulator are NO-independent; however, the vasodilator activity of the compound is greatly diminished when endogenous NO production is inhibited with l-NAME. These data show that BAY 41-8543 has similar vasodilator activity in the pulmonary and systemic vascular beds in the rat.

Effect of Norepinephrine on Circulation of the Dog in Hemorrhagic Shock

1956 ◽  
Vol 186 (1) ◽  
pp. 74-78 ◽  
Author(s):  
E. D. Frank ◽  
H. A. Frank ◽  
S. Jacob ◽  
H. A. E. Weizel ◽  
H. Korman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Renal Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Norepinephrine Infusion ◽  
Pulmonary Arterial

Norepinephrine infusion did not prolong the survival or effect the recovery of dogs in hemorrhagic shock unresponsive to replacement transfusion. During its pressor action in shock, either before or after replacement transfusion, norepinephrine infusion increased coronary, cerebral and adrenal blood flow, reduced renal blood flow, and did not change hepatic blood flow. Cardiac output was increased in oligemic shock but not after blood replacement. Pulmonary arterial pressure and right and left auricular pressures were raised by norepinephrine infusion in all phases of hemorrhagic shock, and calculated pulmonary vascular resistance was reduced.

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