Novel catheterization technique for the in vivo measurement of pulmonary vascular responses in rats

Hyman, Albert L.; Hao, Qingzhong; Tower, Allen; Kadowitz, Philip J.; Champion, Hunter C.; Gümüşel, Bülent; Lippton, Howard

doi:10.1152/ajpheart.1998.274.4.h1218

Cited by 22 publications

(20 citation statements)

References 29 publications

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“…The pulmonary response to U-46619 can be inhibited with thromboxane receptor blocking agents and is not dependent on platelet aggregation or changes in bronchomotor tone, and this agent has greater effect on the pulmonary than systemic vascular bed (13,14,17,24,25). The observation that isradipine has substantial pulmonary vasodilator activity is consistent with studies showing that calcium entry blockers are useful in the treatment of the early phase of primary pulmonary hypertension (31).…”

Section: Discussionsupporting

confidence: 74%

“…A femoral artery was catheterized with PE 50 tubing for the measurement of systemic arterial pressure, and the left jugular and femoral veins were catheterized with PE 50 tubing for intravenous injections or infusions of drugs and fluids. For measurement of pulmonary arterial pressure, a specially designed single lumen 3F catheter with a radio-opaque marker and curved tip was passed from the right jugular vein into the right ventricle and main pulmonary artery under fluoroscopic guidance (Picker Surveyor), as described previously (9,13). Pulmonary and systemic arterial pressures were measured with NAMIC Perceptor transducers (Boston Scientific), digitized by a BIOPAC MP100 data acquisition system, and stored on a Dell PC.…”

Section: Methodsmentioning

confidence: 99%

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

Badejo

Dhaliwal²,

Casey³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Badejo AM Jr, Dhaliwal JS, Casey DB, Gallen TB, Greco AJ, Kadowitz PJ. Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat. Am J Physiol Lung Cell Mol Physiol 295: L828 -L836, 2008. First published August 8, 2008 doi:10.1152/ajplung.00042.2008.-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-Larginine 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 Ca 2ϩ 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.Rho-kinase pathway; Ca 2ϩ sensitization; pulmonary vascular bed; U-46619; isradipine; hypoxia; nitro-L-arginine methyl ester THE SMALL GTP-binding protein Rho and its downstream effector Rho-kinase play an important role in the regulation of vascular smooth muscle tone (3,4,6,18,20,28,34,36). It has been hypothesized that the Rho-kinase system is constitutively active in regulating vasoconstrictor tone and that upregulation of this pathway occurs in a variety of cardiovascular diseases (8,19,21,22,32,33,35). Rho-kinase has been shown to be a potential therapeutic target in a number of cardiovascular diseases including pulmonary hypertension (1,2,10,12,15,16,26,27,29,38). It has been reported that Rho-kinase is upregulated in monocrotaline and chronic hypoxia-induced pulmonary hypertensio...

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Section: Discussionsupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

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

Badejo

Dhaliwal²,

Casey³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The left jugular and femoral veins were catheterized with PE50 tubing for iv administration and infusion of drugs and fluids. For measurement of pulmonary arterial pressure, a 3F catheter with a radiopaque marker and curved tip was passed from the right jugular vein into the main pulmonary artery under fluoroscopic guidance (Picker C-arm fluoroscope), as described previously (9,18). Left ventricular end-diastolic pressure was measured in some experiments by placement of a 3F radiopaque catheter in the chamber under fluoroscopic guidance.…”

Section: Methodsmentioning

confidence: 99%

Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat

Casey¹,

Badejo²,

Dhaliwal³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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PJ. Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat. Am J Physiol Heart Circ Physiol 296: H524 -H533, 2009. First published December 12, 2008 doi:10.1152/ajpheart.00543.2008.-Recent studies show that pulmonary vasodilator responses to nitrite are enhanced by hypoxia. However, the mechanism by which nitrite is converted to vasoactive nitric oxide (NO) is uncertain. In the present study, intravenous injections of sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure were enhanced when tone in the pulmonary vascular bed was increased with U-46619. Under elevated tone conditions, decreases in pulmonary and systemic arterial pressures in response to nitrite were attenuated by allopurinol in a dose that did not alter responses to the NO donors, sodium nitroprusside and diethylamine/NO, suggesting that xanthine oxidoreductase is the major enzyme-reducing nitrite to NO. Ventilation with a 10% O 2 gas mixture increased pulmonary arterial pressure, and the response to hypoxia was enhanced by N G -nitro-L-arginine methyl ester and not altered by allopurinol. This suggests that NO formed by the endothelium and not from the reduction of plasma nitrite modulates the hypoxic pulmonary vasoconstrictor response. Although intravenous injections of sodium nitrite reversed pulmonary hypertensive responses to U-46619, hypoxia, and N G -nitro-L-arginine methyl ester, the pulmonary vasodilator response to nitrite was not altered by ventilation with 10% O2 when baseline pulmonary arterial pressure was increased to similar values in animals breathing room air or the hypoxic gas. These data provide evidence that xanthine oxidoreductase is the major enzyme-reducing nitrite to vasoactive NO, and that this mechanism is not modified by hypoxia. nitric oxide; xanthine oxidoreductase; pulmonary hypertension; nitric oxide synthase ENDOTHELIAL NITRIC OXIDE (NO) formation plays an important role in the regulation of the pulmonary and systemic vascular beds (15, 28). The importance of NO has been demonstrated in experimental animals and in human subjects by the use of NO synthase (NOS) inhibitors (2,15,28). Although NO synthesis is important in the regulation of baseline tone in most vascular beds, the role of NO in the regulation of tone in the pulmonary vascular bed of the rat has been questioned (15). NO once released from the endothelium into the blood reacts rapidly with red cell hemoglobin (14, 21a, 26). Furthermore, NO that escapes hemoglobin scavenging can be oxidized to nitrite (21a). NO formed from nitrite that escapes inactivation relaxes vascular smooth muscle by a cGMP-dependent mechanism (7, 26). It has been reported that plasma nitrite concentrations reflect constitutive NOS activity and correlate with endothelial function (21a). In addition, recent research speculates that nitrite anion represents a storage form of NO that can have important pharmacological actions (13,22). This is...

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“…A similar method has been previously used in the intact rat. 29,30 To study flow-induced vasodilation in the pulmonary vascular bed, the mice were cooled or heated to body temperatures ranging from 29°C to 41°C (as measured by the thermistor probe in the aortic arch), and cardiac output and pulmonary arterial pressure were evaluated in animals 1 day after administration of vehicle, AdCMV␤gal, and AdCMVeNOS. Pressure-flow relationships were derived by plotting pulmonary blood flow (cardiac output) against mean pulmonary arterial pressure.…”

Section: Measurement Of Pulmonary Vascular Responses and Cardiac Outputmentioning

confidence: 99%

Gene Transfer of Endothelial Nitric Oxide Synthase to the Lung of the Mouse In Vivo

Champion

Bivalacqua

D'Souza

et al. 1999

Circulation Research

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Abstract-The effects of transfer of the endothelial nitric oxide synthase (eNOS) gene to the lung were studied in mice.After intratracheal administration of AdCMV␤gal, expression of the ␤-galactosidase reporter gene was detected in pulmonary airway cells, in alveolar cells, and in small pulmonary arteries. Gene expression with AdCMV␤gal peaked 1 day after administration and decayed over a 7-to 14-day period, whereas gene expression after AdRSV␤gal transfection peaked on day 5 and was sustained over a 21-to 28-day period. One day after administration of AdCMVeNOS, eNOS protein levels were increased, and there was a small reduction in mean pulmonary arterial pressure and pulmonary vascular resistance. The pressure-flow relationship in the pulmonary vascular bed was shifted to the right in animals transfected with eNOS, and pulmonary vasodepressor responses to bradykinin and the type V cGMP-selective phosphodiesterase inhibitor zaprinast were enhanced, whereas systemic responses were not altered. Pulmonary vasopressor responses to endothelin-1 (ET-1), angiotensin II, and ventilatory hypoxia were reduced significantly in animals transfected with the eNOS gene, whereas pressor responses to norepinephrine and U46619 were not changed. Systemic pressor responses to ET-1 and angiotensin II were similar in eNOS-transfected mice and in control mice. Intratracheal administration of AdRSVeNOS attenuated the increase in pulmonary arterial pressure in mice exposed to the fibrogenic anticancer agent bleomycin. These data suggest that transfer of the eNOS gene in vivo can selectively reduce pulmonary vascular resistance and pulmonary pressor responses to ET-1, angiotensin II, and hypoxia; enhance pulmonary depressor responses; and attenuate pulmonary hypertension induced by bleomycin. Moreover, these data suggest that in vivo gene transfer may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders. (Circ Res. 1999;84:1422-1432.)Key Words: gene transfer Ⅲ in vivo Ⅲ pulmonary vascular bed Ⅲ mouse Ⅲ nitric oxide L ow-baseline vascular resistance in the lung is maintained by endothelium-dependent and -independent mechanisms. 1-3 Nitric oxide (NO) is released locally and plays an important role in maintaining pulmonary vascular resistance (PVR) at low levels. 1-3 NO is formed from the enzymatic conversion of L-arginine by NO synthase (NOS), which exists in 3 isoforms, endothelial (eNOS; constitutive or NOS III), neural (NOS I), and inducible (iNOS, NOS II). 4 -6 The constitutive forms of the enzyme, eNOS and neural NOS, are regulated by calcium and calmodulin. 4 -6 Although iNOS has been shown to be constitutively expressed and present in cells exposed to cytokines, expression is upregulated in pathophysiological conditions. 4 -6 NO binds to the ferrous heme moiety of soluble guanylate cyclase in vascular smooth muscle and platelets to increase intracellular cGMP levels, inhibit platelet aggregation, and relax vascular smooth muscle. [1][2][3][4][5][6][7] NO is believed to play an important role ...

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Novel catheterization technique for the in vivo measurement of pulmonary vascular responses in rats

Cited by 22 publications

References 29 publications

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

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

Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat

Gene Transfer of Endothelial Nitric Oxide Synthase to the Lung of the Mouse In Vivo

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