Pulmonary vascular alpha 1-adrenoreceptor activity in conscious dogs after left lung autotransplantation

1993 ◽  
Vol 74 (2) ◽  
pp. 733-741 ◽  
Author(s):  
K. Nishiwaki ◽  
D. P. Nyhan ◽  
R. S. Stuart ◽  
P. M. Desai ◽  
W. P. Peterson ◽  
...  
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Left Lung ◽  
Conscious Dogs ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Pressure Flow ◽  
Vascular Regulation

We investigated the extent to which sympathetic alpha 1-adrenoreceptor activation is involved in chronic pulmonary vascular regulation in conscious dogs after left lung autotransplantation (LLA). Continuous left pulmonary vascular pressure-flow plots were generated in conscious dogs 3–4 wk post-LLA and in identically instrumented conscious dogs not subjected to LLA (sham-operated controls). LLA resulted in a marked upward shift in the baseline left pulmonary vascular pressure-flow relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The sympathetic alpha 1-adrenoreceptor antagonist prazosin partially reversed (P < 0.01) the LLA-induced increase in pulmonary vascular resistance. Circulating concentrations of norepinephrine and epinephrine at 2 and 4 wk post-LLA were not significantly different from values measured in control dogs. However, the dose-response relationship to the exogenous administration of the sympathetic alpha 1-adrenoreceptor agonist phenylephrine was shifted (P < 0.05) to the left post-LLA compared with control, which indicates an increase in pulmonary vascular reactivity to alpha 1-adrenoreceptor activation. This effect was not due to a generalized increase in pulmonary vascular reactivity to vasoconstrictor stimuli because the dose-response relationship to the thromboxane analogue U-46619 was not significantly altered post-LLA compared with control. Thus LLA results in a chronic increase in pulmonary vascular resistance in conscious dogs. A component of the increase in pulmonary vascular resistance resulting from LLA is mediated by an enhanced reactivity to sympathetic alpha 1-adrenoreceptor activation.

Prolonged pulmonary vascular hyperreactivity in conscious dogs after cardiopulmonary bypass

1994 ◽  
Vol 77 (4) ◽  
pp. 1584-1590 ◽  
Author(s):  
D. P. Nyhan ◽  
J. M. Redmond ◽  
A. M. Gillinov ◽  
K. Nishiwaki ◽  
P. A. Murray
Keyword(s):  
Cardiopulmonary Bypass ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Vascular Reactivity ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Conscious Dogs ◽  
Dose Response Relationship ◽  
Vascular Regulation ◽  
Vasoconstrictor Response

Although cardiopulmonary bypass (CPB) is required in all surgical procedures involving open-heart surgery, the extent to which CPB alters pulmonary vascular regulation has not been systematically investigated. Our objectives were to investigate the acute, subacute, and chronic effects of CPB on the left pulmonary vascular pressure-flow (LP-Q) relationship in conscious dogs. Continuous LP-Q plots were generated in chronically instrumented conscious dogs 2–4 days pre-CPB and again 4 h and 1, 2, 7, and 14 days after 2.5 h of closed-chest hypothermic CPB. In addition, pulmonary vascular reactivity was assessed by examining the dose-response relationship to the thromboxane analogue U-46619 pre- and post-CPB. CPB resulted in an acute (4 h post-CPB) shift in the baseline LP-Q relationship, indicating an increase in pulmonary vascular resistance (P < 0.01). The baseline LP-Q relationship returned to pre-CPB values by 1 day post-CPB. Despite this return of the baseline LP-Q relationship to pre-CPB values, the pulmonary vasoconstrictor response to U-46619 was markedly potentiated 2 days post-CPB compared with the pre-CPB response (P < 0.01). This enhanced pulmonary vasoconstrictor response to U-46619 was still apparent 7 days post-CPB (P < 0.01) but was not evident 14 days post-CPB. These results indicate that CPB results in a pronounced, but transient, increase in pulmonary vascular resistance. Moreover, CPB causes a protracted increase in pulmonary vascular reactivity even when the baseline LP-Q relationship has returned to pre-CPB values.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vascular beta-adrenoreceptor activity in conscious dogs after left lung autotransplantation

1993 ◽  
Vol 75 (1) ◽  
pp. 256-263 ◽  
Author(s):  
K. Nishiwaki ◽  
P. Rock ◽  
R. S. Stuart ◽  
D. P. Nyhan ◽  
W. P. Peterson ◽  
...  
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Vascular Reactivity ◽  
Left Lung ◽  
Conscious Dogs ◽  
Control Group ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilator ◽  
Chronic Denervation

Our objective was to determine whether chronic denervation associated with left lung autotransplantation (LLA) results in an alteration in sympathetic beta-adrenoreceptor regulation of the pulmonary circulation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 2–4 wk post-LLA and in sham-operated control conscious dogs. We tested the hypothesis that endogenous sympathetic beta-adrenoreceptor activation via circulating catecholamines acted to attenuate the chronic increase in pulmonary vascular resistance post-LLA. Administration of the sympathetic beta-adrenoreceptor antagonist propranolol had no significant effect on the LPQ relationship post-LLA. We also tested the hypothesis that pulmonary vascular reactivity to sympathetic beta-adrenoreceptor activation would be increased post-LLA. The thromboxane analogue U-46619 was used to acutely preconstrict (P < 0.01) the pulmonary circulation in control dogs; this preconstriction shifted the LPQ relationship to the same position measured post-LLA. Under these conditions, cumulative doses of the beta-adrenoreceptor agonist isoproterenol caused pulmonary vasodilation (P < 0.01) in the control group but had no effect post-LLA. However, after acute preconstriction with U-46619, the pulmonary vasodilator response (P < 0.01) to isoproterenol post-LLA was not significantly different from that in the control group. These differential responses to isoproterenol with and without acute preconstriction indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is mediated by passive nonvasoactive mechanisms. Moreover, sympathetic beta-adrenoreceptor reactivity of the pulmonary circulation is not enhanced by chronic denervation resulting from the LLA procedure.

Pulmonary Vascular Effects of Isoflurane Anesthesia after Left Lung Autotransplantation in Chronically Instrumented Dogs

1996 ◽  
Vol 85 (3) ◽  
pp. 592-599. ◽  
Author(s):  
Paul F. Lennon ◽  
Paul A. Murray
Keyword(s):  
Lung Transplantation ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Left Lung ◽  
Pressure Flow ◽  
Isoflurane Anesthesia ◽  
Vasoconstrictor Response ◽  
Chronically Instrumented Dogs ◽  
Conscious Control

Background Single lung transplantation has become a viable therapy for treatment of end-stage pulmonary disease. We previously observed that left lung autotransplantation (LLA) results in a chronic increase in pulmonary vascular resistance and enhanced pulmonary vascular reactivity to sympathetic alpha adrenoreceptor activation. The effects of inhalational anesthetics on the pulmonary circulation after lung transplantation have not been investigated. In the current study, the authors tested the hypothesis that isoflurane anesthesia, known to cause systemic vasodilation, would exert a vasodilator influence on the baseline pulmonary circulation after LLA. In addition, they tested the hypothesis that isoflurane anesthesia, known to attenuate the systemic vasoconstrictor response to sympathetic alpha adrenoreceptor agonists, would reduce the magnitude of the pulmonary vasoconstrictor response to sympathetic alpha adrenoreceptor activation after LLA. Methods Left pulmonary vascular pressure-flow (LPQ) plots were generated in chronically instrumented dogs by measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during inflation of a hydraulic occluder implanted around the right main pulmonary artery. Left pulmonary vascular pressure-flow plots were generated in 8 dogs 2-5 weeks after LLA in the conscious and isoflurane-anesthetized states at baseline, after beta adrenoreceptor block with propranolol, and during the cumulative administration of the alpha agonist, phenylephrine. Left pulmonary vascular pressure-flow plots also were generated in eight conscious, sham-operated control dogs at baseline, after beta block, and during phenylephrine administration. Results Compared with conscious control dogs, LLA resulted in a leftward shift (P &lt; 0.01) in the baseline left pulmonary vascular pressure-flow relation, indicating chronic pulmonary vasoconstriction. Despite the enhanced level of pulmonary vasomotor tone after LLA, isoflurane did not exert a vasodilator influence on the baseline left pulmonary vascular pressure-flow relation. The pulmonary vasoconstrictor response to phenylephrine was enhanced (P &lt; 0.01) after LLA compared with the response measured in conscious control dogs. The magnitude of the pulmonary vasoconstrictor response to phenylephrine after LLA was not attenuated during isoflurane anesthesia. Conclusions Isoflurane anesthesia does not exert a vasodilator influence on the pulmonary circulation in the setting of increased pulmonary vascular resistance after LLA. In addition, in contrast to previous studies of the systemic circulation, isoflurane does not attenuate the enhanced pulmonary vasoconstrictor response to sympathetic alpha adrenoreceptor activation after LLA.

Abnormal responses to pulmonary vasodilators in conscious dogs after left lung autotransplantation

1993 ◽  
Vol 264 (3) ◽  
pp. H917-H925 ◽  
Author(s):  
K. Nishiwaki ◽  
D. P. Nyhan ◽  
R. S. Stuart ◽  
P. Rock ◽  
P. M. Desai ◽  
...  
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Left Lung ◽  
Conscious Dogs ◽  
Control Group ◽  
Vasomotor Tone ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilators ◽  
Pulmonary Vasodilator

We investigated the extent to which left lung autotransplantation (LLA) alters endothelium-dependent (bradykinin and acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in the pulmonary circulation of conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 3–4 wk post-LLA and in sham-operated controls. LLA resulted in a marked upward shift in the baseline LPQ relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The thromboxane analogue, U-46619, was used to acutely preconstrict the pulmonary circulation in control dogs, which shifted the control LPQ relationship to the same position measured post-LLA. Under these circumstances, bradykinin, acetylcholine, and nitroprusside caused pulmonary vasodilation in the control group, whereas these responses were either attenuated or reversed to vasoconstriction post-LLA. After acute preconstriction with U-46619 post-LLA, the pulmonary vasodilator responses to bradykinin and acetylcholine were again attenuated, but the response to nitroprusside was unaltered compared with control. These results indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is passively mediated and does not reflect an active increase in baseline vasomotor tone. Moreover, LLA results in an impairment in endothelium-dependent, but not endothelium-independent, pulmonary vasodilation in conscious dogs.

Humoral pulmonary vasoregulation in conscious dogs after left lung autotransplantation

1994 ◽  
Vol 76 (2) ◽  
pp. 902-908 ◽  
Author(s):  
P. M. Desai ◽  
K. Nishiwaki ◽  
R. S. Stuart ◽  
D. P. Nyhan ◽  
P. A. Murray
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Left Lung ◽  
Receptor Activation ◽  
Conscious Dogs ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Control Group ◽  
Ang Ii ◽  
Receptor Block ◽  
Pathway Inhibition

We investigated the roles of cyclooxygenase metabolites, arginine vasopressin (AVP) and angiotensin II (ANG II), as mediators of the chronic increase in pulmonary vascular resistance associated with left lung autotransplantation (LLA) in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q) plots were generated in conscious dogs 2- to 5-wk post-LLA and in sham-operated control conscious dogs. LLA resulted in a marked shift (P < 0.01) in the LP-Q relationship as reflected by an approximate doubling of the pulmonary vascular pressure gradient at each common value of left pulmonary blood flow compared with the control group. Cyclooxygenase pathway inhibition (indomethacin) and AVP V1-receptor block had no effect on the LP-Q relationship post-LLA. Angiotensin-converting enzyme inhibition (captopril) also failed to reverse the increase in pulmonary vascular resistance post-LLA. Because captopril has the dual effect of inhibiting the production of ANG II and the degradation of bradykinin, additional studies utilizing a selective ANG II receptor antagonist were performed. ANG II receptor block (saralasin) significantly altered the LP-Q relationship post-LLA to cause active pulmonary vasodilation (P < 0.01). Thus, the chronic increase in pulmonary vascular resistance post-LLA is not mediated by metabolites of the cyclooxygenase pathway or AVP V1-receptor activation. A significant component of the increase in pulmonary vascular resistance resulting from LLA is mediated by ANG II. The differential responses to captopril and saralasin may imply a pulmonary vasoregulatory role for bradykinin post-LLA.

A SUBCUTANEOUS INJECTION ASSAY FOR ANTI-ANDROGENS IN THE CHICK

1962 ◽  
Vol 41 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Subcutaneous Injection ◽  
Response Relationship ◽  
Dose Response Relationship

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.

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