Analysis of systemic and pulmonary vascular responses to PACAP and VIP: role of adrenal catecholamines

1992 ◽  
Vol 263 (6) ◽  
pp. H1659-H1669 ◽  
Author(s):  
R. K. Minkes ◽  
T. J. McMahon ◽  
T. R. Higuera ◽  
W. A. Murphy ◽  
D. H. Coy ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Pressor Response ◽  
Venous Pressure ◽  
Vascular Responses ◽  
Intravenous Injections ◽  
Pressor Responses ◽  
Pituitary Adenylate Cyclase ◽  
Pulmonary Arterial ◽  
Dose Dependent

Systemic and pulmonary vascular responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide with 68% sequence homology to vasoactive intestinal peptide (VIP), were investigated in the anesthetized cat. Intravenous injections of PACAP in doses of 0.1–3.0 nmol/kg produced decreases in arterial pressure (AP) at low doses and biphasic changes (decreases followed by increases) at higher doses, which were accompanied by increases in central venous pressure (CVP) and cardiac output (CO), and decreases and biphasic changes in systemic vascular resistance (SVR). In contrast, VIP in doses of 0.1-3.0 nmol/kg produced only dose-dependent decreases in AP and SVR and produced little change in CVP and CO. PACAP produced increased pulmonary arterial pressure (PAP), left atrial pressure (LAP), and increases in pulmonary vascular resistance (PVR). PACAP increased heart rate (HR) and right ventricular contractile force (RVCF), while VIP had no effect. Increases in AP and SVR in response to PACAP were changed to decreases following the administration of phentolamine or after adrenalectomy. Under constant flow conditions, PACAP and VIP produced dose-dependent decreases in lobar arterial pressure when tone was elevated, with PACAP being threefold more potent than VIP. Meclofenamate and nitro-L-arginine methyl ester (L-NAME) had no effect on pulmonary responses to the peptides. PACAP produced dose-dependent biphasic changes in hindquarters perfusion pressure, whereas VIP produced only decreases that were unchanged by indomethacin, L-NAME, and glibenclamide. Phentolamine and adrenalectomy eliminated the hindquarters pressor response to PACAP and D-Phe2-VIP, a VIP antagonist, reduced responses to VIP but not to PACAP. These data suggest that responses to PACAP and VIP are mediated by distinct receptors and that pressor responses to PACAP are due to the release of catecholamines from the adrenal gland.

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.

Mechanisms of pressor response produced by stimulation of nucleus ambiguus

1990 ◽  
Vol 259 (5) ◽  
pp. R955-R962
Author(s):  
B. H. Machado ◽  
M. J. Brody
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Pressor Response ◽  
Nucleus Ambiguus ◽  
Ventrolateral Medulla ◽  
Pressor Responses ◽  
Regional Vascular Resistance ◽  
Parasympathetic Control ◽  
Renal Vascular ◽  
Stimulation Of

We showed previously that activation of nucleus ambiguus (NA) induced bradycardia and increased arterial pressure. In this study, we compared responses produced by electrical and chemical (glutamate) stimulation of NA and adjacent rostral ventrolateral medulla (RVLM). Equivalent pressor responses were elicited from both areas. However: 1) The response from RVLM was elicited at a lower frequency. 2) Regional vascular resistance changes were different, i.e., electrical stimulation of NA increased vascular resistance in hindquarters much more than the renal and mesenteric beds. In contrast, electrical and chemical stimulation of RVLM produced a more prominent effect on the renal vascular bed. 3) Bradycardia was elicited from NA at lower current intensity. 4) Glutamate produced bradycardia only when injected into NA. Studies in rats with sinoaortic deafferentation showed that bradycardic response to activation of NA was only partly reflex in origin. We conclude that 1) NA and RVLM control sympathetic outflow to regional vascular beds differentially and 2) the NA region involves parasympathetic control of heart rate and sympathetic control of arterial pressure.

Comparison of responses to sarafotoxins 6a and 6c in pulmonary and systemic vascular beds

1992 ◽  
Vol 262 (3) ◽  
pp. H852-H861
Author(s):  
R. K. Minkes ◽  
J. A. Bellan ◽  
T. R. Higuera ◽  
P. J. Kadowitz
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Perfusion Pressure ◽  
Venous Pressure ◽  
Constant Flow ◽  
Flow Conditions ◽  
Arterial Perfusion ◽  
Intravenous Injections ◽  
Autonomic Reflexes ◽  
Pressure Changes

Cardiovascular and pulmonary responses to sarafotoxin (S) 6a and S6c were investigated in the anesthetized cat. Intravenous injections of the peptides in doses of 0.1-1.0 nmol/kg caused decreases or biphasic changes in arterial pressure (AP) and increases in central venous pressure, pulmonary arterial pressure (PAP), and cardiac output (CO). Secondary decreases in CO were observed in response to higher doses, and biphasic changes in systemic (SVR) and pulmonary (PVR) vascular resistances were observed. Under constant-flow conditions, the peptides only increased pulmonary lobar arterial perfusion pressure and lobar vascular resistance. AP responses to S6a, S6c, endothelin (ET)-1, ET-2, vasoactive intestinal contractor (VIC), and Lys7-ET-1 were similar, whereas AP responses to S6b and ET-3 were similar. S6a, S6b, S6c, ET-1, ET-2, ET-3, VIC, Lys7-ET-1, and big ET-1 increased PAP. S6a and S6c increased distal aortic and superior mesenteric arterial (SMA) blood flow and caused biphasic changes at the highest doses. Under constant-flow conditions, S6a and S6c produced dose-dependent biphasic changes in hindquarters perfusion pressure. Changes in SVR and PVR in response to the peptide were not affected by hexamethonium, glyburide, or meclofenamate, indicating that responses are independent of autonomic reflexes, activation of ATP-regulated K+ channels, or release of cyclooxygenase products. In contrast, N-nitro-L-arginine methyl ester decreased hindquarters vasodilator response to S6a and S6c. The present data show that S6a and S6c produce both vasodilation and vasoconstriction in the systemic vascular bed and increase lobar vascular resistance and that hindquarters vasodilator responses are mediated, in part, by the release of endothelium-derived relaxing factor.

Comparative responses to endothelin 2 and sarafotoxin 6b in systemic vascular bed of cats

1990 ◽  
Vol 258 (5) ◽  
pp. H1550-H1558
Author(s):  
R. K. Minkes ◽  
P. J. Kadowitz
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Venous Pressure ◽  
Cardiovascular Responses ◽  
Aortic Blood Flow ◽  
Vasodilator Activity ◽  
Pulmonary Arterial ◽  
Vascular Beds ◽  
Dose Dependent ◽  
Higher Doses

Cardiovascular responses to endothelin 2 (ET-2) and sarafotoxin 6b (S6b) were investigated in the cat. ET-2 (0.1-1 nmol/kg iv) decreased or elicited biphasic changes in arterial pressure (AP), whereas S6b (0.1-1 nmol/kg iv) only decreased AP. Central venous pressure (CVP), cardiac output (CO), and pulmonary arterial pressure (PAP) were increased. ET-2 produced biphasic changes in systemic vascular resistance (SVR), whereas S6b decreased SVR at the two lower doses and caused a biphasic change at the 1 nmol/kg dose. The effects of ET-1 and ET-2 were similar, whereas the effects of S6b were similar to ET-3. ET-2 and S6b had small effects on right ventricular contractile force and caused transient increases in heart rate. Distal aortic blood flow was increased in response to all doses of both peptides, whereas increases in carotid blood flow were observed only in response to the higher doses of ET-2 and S6b. ET-2 produced dose-dependent decreases in superior mesenteric artery (SMA) blood flow, whereas decreases in SMA flow in response to S6b were observed only at the 1 nmol/kg dose. Renal blood flow was decreased significantly only at the higher doses of ET-2 and S6b. The present data show that ET-2 and S6b can produce both vasodilation and vasoconstriction in the systemic and regional vascular beds of the cat and demonstrate previously unrecognized vasodilator activity in response to S6b. It is concluded that ET-2 and S6b produce complex cardiovascular responses in the anesthetized cat.

Correlation of acute with chronic hypoxic pulmonary hypertension in cattle

1975 ◽  
Vol 38 (3) ◽  
pp. 495-498 ◽  
Author(s):  
D. H. Will ◽  
J. L. Hicks ◽  
C. S. Card ◽  
J. T. Reeves ◽  
A. F. Alexander
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Acute Hypoxia ◽  
Common Mechanism ◽  
Mean Pulmonary Arterial Pressure ◽  
Pressor Responses ◽  
Pulmonary Arterial ◽  
Highly Correlated

We investigated acute and chronic hypoxic pulmonary pressor responses in two groups of calves, one bred to be susceptible, the other resistant to high-altitude pulmonary hypertension. Twelve 5-mo-old susceptible calves residing at 1,524 m increased their mean pulmonary arterial pressure from 26 +/- 2 (SE) to 55 +/- 4 mmHg during 2 h at a simulated altitude of 4,572 m. In 10 resistant calves pressure increased from 22 +/- 1 to 37 +/- 2 mmHg. Five calves were selected from each group for further study. When 9 mo old, the 5 susceptible calves again showed a greater pressor response to acute hypoxia (27 +/- 1 to 55 +/- 4 mmHg) than did 5 resistant calves (23 +/- 1 to 41 +/- 3 mmHg). When 12 mo old, the 5 susceptible calves also developed a greater increase in pulmonary arterial pressure (21 +/- 2 to 9 +/- 4 mmHg) during 18 days at 4,572 m than did the 5 resistant calves (21 +/- 1 to 64 +/- 4 mmHg). Acute and chronic hypoxic pulmonary pressor responses were highly correlated (r = 0.91; P less than 0.001) indicating that they were probably produced through a common mechanism.

Pulmonary vascular reactivity and hemodynamic changes in elastase-induced emphysema in hamsters

1992 ◽  
Vol 73 (4) ◽  
pp. 1474-1480 ◽  
Author(s):  
C. M. Tseng ◽  
S. Qian ◽  
W. Mitzner
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Ventricular Hypertrophy ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Pressor Responses ◽  
Pulmonary Arterial

Changes in pulmonary hemodynamics and vascular reactivity in emphysematous hamsters were studied in an isolated lung preparation perfused at constant flow with blood and 3% dextran. Hamsters were treated with intratracheal porcine pancreatic elastase at 70 days of age, and experimental studies were conducted at 1, 3, and 8 mo after treatment. Baseline pulmonary arterial pressure in elastase-treated lungs was increased compared with saline-treated control lungs 1 mo after treatment, but this increase did not progress at 3 and 8 mo. Increases in pulmonary arterial pressure in elastase-treated lungs were temporally correlated with the morphological development of emphysema and right ventricular hypertrophy; both of these were evident at 1 mo after treatment and showed little change thereafter. Pressor responses to hypoxia and angiotensin II were not different between elastase-treated and control lungs at 1 and 3 mo. At 8 mo, however, pressor responses in emphysematous lungs to 0% O2 (but not to angiotensin II) were significantly increased. This was the result of a lack of the normal age-related fall in the hypoxic pressor response. Our results suggest that the right ventricular hypertrophy found in these emphysematous animals results from a chronically increased pulmonary vascular resistance. Furthermore, increases in pulmonary vascular resistance in the early development of emphysema are likely a result of the loss of vascular beds and supporting connective tissue.

Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia

1988 ◽  
Vol 65 (5) ◽  
pp. 1975-1983 ◽  
Author(s):  
S. Adnot ◽  
P. E. Chabrier ◽  
C. Brun-Buisson ◽  
I. Viossat ◽  
P. Braquet
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Atrial Natriuretic Factor ◽  
Pressor Response ◽  
Systemic Arterial Pressure ◽  
Pulmonary Hemodynamics ◽  
Natriuretic Factor ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Atrial Natriuretic

The influence of endogenous and exogenous atrial natriuretic factor (ANF) on pulmonary hemodynamics was investigated in anesthetized pigs during both normoxia and hypoxia. Continuous hypoxic ventilation with 11% O2 was associated with a uniform but transient increase of plasma immunoreactive (ir) ANF that peaked at 15 min. Plasma irANF was inversely related to pulmonary arterial pressure (Ppa; r = -0.66, P less than 0.01) and pulmonary vascular resistance (PVR; r = -0.56, P less than 0.05) at 30 min of hypoxia in 14 animals; no such relationship was found during normoxia. ANF infusion after 60 min of hypoxia in seven pigs reduced the 156 +/- 20% increase in PVR to 124 +/- 18% (P less than 0.01) at 0.01 microgram.kg-1.min-1 and to 101 +/- 15% (P less than 0.001) at 0.05 microgram.kg-1.min-1. Cardiac output (CO) and systemic arterial pressure (Psa) remained unchanged, whereas mean Ppa decreased from 25.5 +/- 1.5 to 20.5 +/- 15 mmHg (P less than 0.001) and plasma irANF increased two- to nine-fold. ANF infused at 0.1 microgram.kg-1.min-1 (resulting in a 50-fold plasma irANF increase) decreased Psa (-14%) and reduced CO (-10%); systemic vascular resistance (SVR) was not changed, nor was a further decrease in PVR induced. No change in PVR or SVR occurred in normoxic animals at any ANF infusion rate. These results suggest that ANF may act as an endogenous pulmonary vasodilator that could modulate the pulmonary pressor response to hypoxia.

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.

Analysis of pulmonary and systemic vascular responses to platelet-activating factor in the cat

1992 ◽  
Vol 263 (1) ◽  
pp. H234-H243
Author(s):  
J. A. Bellan ◽  
R. K. Minkes ◽  
J. S. Hood ◽  
T. J. McMahon ◽  
T. R. Higuera ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Vascular Resistance ◽  
Platelet Activating Factor ◽  
Cyclooxygenase Inhibitors ◽  
Vascular Responses ◽  
Intravenous Injections ◽  
Vascular Bed ◽  
Cellular Aggregation ◽  
Thromboxane Receptor Antagonist

Pulmonary and systemic vascular responses to platelet-activating factor (PAF) were investigated in the anesthetized cat. Intravenous injections of PAF decreased arterial pressure, increased pulmonary arterial pressure, and caused small but significant decreases in right and left atrial pressures. A transient increase in cardiac output was followed by a secondary decrease, and heart rate was increased. Pulmonary vascular resistance (PVR) was increased, systemic vascular resistance (SVR) was reduced, and changes in PVR and SVR in response to PAF were blocked by the novel PAF receptor antagonist, BN 50730. Under constant-flow conditions PAF dilated the hindlimb vascular bed in a dose-related manner, whereas in the pulmonary lobar vascular bed, PAF caused dose-related increases in perfusion pressure. Hindlimb and lobar vascular responses to PAF were blocked by BN 50730 in a selective manner, whereas cyclooxygenase inhibitors had no effect on responses to the phospholipid mediator. Hindlimb vasodilator responses to PAF were reduced by N omega-nitro-L-arginine in a dose that blocked the response to acetylcholine but did not decrease responses to prostaglandin E1 or nitroprusside. Increases in lobar arterial pressure in response to PAF were not altered by treatment with a thromboxane receptor antagonist, when the lung was perfused with a low-molecular-weight dextran solution, or when ventilation to the lobe was interrupted. These data suggest that the release of cyclooxygenase products, activation of thromboxane A2 receptors, cellular aggregation, release of leukocyte or platelet mediators, or changes in bronchomotor tone do not contribute to the pulmonary vasoconstrictor response to PAF and that the hindlimb vasodilator response to the phospholipid mediator is dependent in part on the release of endothelium-derived relaxing factor.

Analysis of pulmonary and systemic vascular responses to cromakalim, an activator of K+ATP channels

1991 ◽  
Vol 260 (3) ◽  
pp. H957-H966 ◽  
Author(s):  
R. K. Minkes ◽  
P. Kvamme ◽  
T. R. Higuera ◽  
B. D. Nossaman ◽  
P. J. Kadowitz
Keyword(s):  
Arterial Pressure ◽  
Perfusion Pressure ◽  
Antihypertensive Agents ◽  
Blocking Agent ◽  
High Dose ◽  
Arterial Perfusion ◽  
Intravenous Injections ◽  
Vasodilator Activity ◽  
Pulmonary Arterial ◽  
Dose Dependent

Cardiovascular and pulmonary responses to cromakalim, a member of a novel class of antihypertensive agents that open ATP-sensitive K+ (K+ATP) channels, were investigated in the anesthetized cat. Intravenous injections of cromakalim in doses of 30-300 micrograms/kg decreased arterial pressure (AP), pulmonary arterial pressure (PAP), and increased cardiac output (CO), while producing small changes in right and left atrial pressures. Pulmonary and systemic vascular resistances were decreased and vasodilator responses to cromakalim were blocked by glybenclamide, a K+ATP channel-blocking agent. The low dose of cromakalim caused a reflex increase in heart rate (HR) and right ventricular contractile force (RVCF), whereas the high dose decreased HR and RVCF. Under constant-flow conditions the K+ATP channel opener caused dose-dependent decreases in hindquarters perfusion pressure, and when tone was elevated in the pulmonary vascular bed, dose-dependent decreases in pulmonary lobar arterial perfusion pressure. Hindquarters and pulmonary lobar vasodilator responses to cromakalim were inhibited in a specific manner by glybenclamide. The present data show that cromakalim has significant vasodilator activity in both the systemic and pulmonary vascular beds and suggest that responses to this agent result from activation of glybenclamide-sensitive K+ATP channels. These data show that cromakalim can cause substantial decreases in systemic and pulmonary vascular resistance in a dose that has little effect on RVCF.

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