Contractile effects of 5-hydroxytryptamine in isolated intrapulmonary arteries and veins

1981 ◽  
Vol 59 (2) ◽  
pp. 157-162 ◽  
Author(s):  
Carl A. Gruetter ◽  
Louis J. Ignarro ◽  
Albert L. Hyman ◽  
Philip J. Kadowitz
Keyword(s):  
Vascular Resistance ◽  
Pulmonary Thromboembolism ◽  
Force Generation ◽  
Contractile Responses ◽  
Adrenergic Mechanisms ◽  
Blocking Agents ◽  
Vascular Bed ◽  
Arteries And Veins ◽  
Pulmonary Vascular Bed

The contractile effects of serotonin (5-hydroxytryptamine, 5-HT) were compared in helical strips of intrapulmonary artery (IPA) and vein (IPV) isolated from lungs of dog, rabbit, cow, and man. 5-HT (10−8–10−4 M) increased force generation by IPA and IPV from the four species in a concentration-related manner. Sensitivities to 5-HT of IPA and IPV from the four species were similar, with median effective concentrations ranging from 3 × 10−8 to 3 × 10−7 M. However, maximal contractile responses to 5-HT relative to those elicited by potassium were greater in canine and human IPA and bovine IPA and IPV than in rabbit IPA and IPV and canine and human IPV. Results obtained using specific pharmacologic blocking agents suggest that 5-HT-induced contraction of canine and rabbit intrapulmonary vessels does not involve α-adrenergic mechanisms except, possibly, in rabbit IPV. The contractile effects of 5-HT observed in the present study suggest that 5-HT released from platelets could contribute to increased vascular resistance during pulmonary thromboembolism by actively constricting arterial and venous segments of the pulmonary vascular bed in a variety of species, including man.

Pulmonary vasodilator responses to vasoactive intestinal peptide in the cat

1985 ◽  
Vol 58 (5) ◽  
pp. 1723-1728 ◽  
Author(s):  
P. A. Nandiwada ◽  
P. J. Kadowitz ◽  
S. I. Said ◽  
M. Mojarad ◽  
A. L. Hyman
Keyword(s):  
Arterial Pressure ◽  
Vasoactive Intestinal Peptide ◽  
Vascular Resistance ◽  
Vascular Tone ◽  
Base Line ◽  
Vascular Bed ◽  
Pulmonary Vasodilator ◽  
Vasodilator Activity ◽  
Adrenergic Mechanism ◽  
Pulmonary Vascular Bed

We investigated the effects of vasoactive intestinal peptide (VIP) in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow when pulmonary vascular tone was at base-line levels and when vascular resistance was elevated. Under base-line conditions, VIP caused small but significant reductions in lobar arterial pressure without affecting left atrial pressure. Decreases in lobar arterial pressure in response to VIP were greater and were dose related when lobar vascular resistance was increased by intralobar infusion of U 46619, a stable prostaglandin endoperoxide analogue. Acetylcholine and isoproterenol also caused significant decreases in lobar arterial pressure under base-line conditions, and responses to these agents were enhanced when lobar vascular tone was elevated. Moreover, when doses of these agents are expressed in nanomoles, acetylcholine and isoproterenol were more potent than VIP in decreasing lobar arterial pressure. Responses to VIP were longer in duration with a slower onset than were responses to acetylcholine or isoproterenol. Pulmonary vasodilator responses to VIP were unchanged by indomethacin, atropine, or propranolol. The present data demonstrate that VIP has vasodilator activity in the pulmonary vascular bed and that responses are dependent on the existing level of vasoconstrictor tone. These studies indicate that this peptide is less potent than acetylcholine or isoproterenol in dilating the feline pulmonary vascular bed and that responses to VIP are not dependent on a muscarinic or beta-adrenergic mechanism or release of a dilator prostaglandin.

Pulmonary vasodilator responses to adrenomedullin are reduced by NOS inhibitors in rats but not in cats

1996 ◽  
Vol 270 (5) ◽  
pp. L782-L789 ◽  
Author(s):  
B. D. Nossaman ◽  
C. J. Feng ◽  
A. D. Kaye ◽  
B. DeWitt ◽  
D. H. Coy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amino Acid ◽  
Vascular Resistance ◽  
Rat Lung ◽  
Related Peptide ◽  
Vascular Bed ◽  
Pulmonary Vasodilator ◽  
Vasodilator Activity ◽  
Carboxy Terminal ◽  
Pulmonary Vascular Bed

Responses to and the mechanism of action of adrenomedullin (ADM), the carboxy-terminal fragments of ADM, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the pulmonary vascular bed of the rat. Under conditions of elevated tone and controlled pulmonary blood flow in the isolated blood-perfused rat lung, injections of ADM, the 15-52 amino acid carboxy-terminal ADM analogue (ADM15-52), and CGRP caused dose-related decreases in pulmonary arterial perfusion pressure. In contrast, the carboxy-terminal 22-52 and 40-52 amino acid fragments had no consistent vasodilator activity. After administration of the nitric oxide synthase inhibitors, N omega-nitro-L-arginine benzyl ester or N omega-nitro-L-arginine methyl ester (L-NAME), pulmonary vasodilator responses to ADM, to ADM15-52, to CGRP, to acetylcholine, and to bradykinin were significantly decreased in the rat, whereas vasodilator responses to isoproterenol and nitroglycerin were not changed. However, in the pulmonary vascular bed of the cat, L-NAME had no significant effect on vasodilator responses to ADM in doses that attenuated vasodilator responses to acetylcholine and bradykinin. L-NAME had no effect on responses to isoproterenol or nitric oxide. When the relative vasodilator activity of the active peptides was compared, ADM15-52 was approximately three-fold less potent than ADM, and ADM was threefold less potent than CGRP in decreasing pulmonary vascular resistance in the rat lung. When vasodilator responses were compared in the rat and cat, ADM was threefold more potent in decreasing pulmonary vascular vascular resistance in the cat than in the rat, and vasodilator responses to ADM were independent of the intervention used to raise tone in the rat. The present data demonstrate that ADM and ADM15-52 have significant vasodilator activity in the pulmonary vascular bed of the rat, and that responses to ADM, ADM15-52, and CGRP are dependent on the release of nitric oxide in the rat. The present results indicate that pulmonary vasodilator responses to ADM are not dependent on the release of nitric oxide in the cat and suggest that responses to the peptide are mediated by different mechanisms in the pulmonary vascular bed of the rat and cat.

Basis for the selective reduction of pulmonary vascular resistance in humans during infusion of adenosine

1994 ◽  
Vol 76 (2) ◽  
pp. 724-730 ◽  
Author(s):  
D. B. Utterback ◽  
E. D. Staples ◽  
S. E. White ◽  
J. A. Hill ◽  
L. Belardinelli
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Artery Bypass ◽  
Plasma Concentrations ◽  
Resistance Index ◽  
Selective Reduction ◽  
Systemic Circulation ◽  
Vascular Bed ◽  
The Right ◽  
Pulmonary Vascular Bed

The objective of this study was to demonstrate the basis for the selective reduction of pulmonary vascular resistance by intravenous infusion of adenosine. Secondary objectives of the study were to determine the rate of central infusion of adenosine at which the nucleoside appears in the systemic circulation and to relate this to hemodynamic events. Plasma concentrations of adenosine in the right and left atria were measured during peripheral (5 patients) and central (12 patients) infusions of adenosine in adults with normal pulmonary arterial pressures undergoing coronary artery bypass surgery. The hemodynamic effects of central (right ventricle) infusion of adenosine were also examined. The extraction of adenosine across the pulmonary vascular bed was found to be 73.6 +/- 4.8%. The mean maximal decrease in pulmonary vascular resistance index, 48.8 +/- 9.6%, occurred at an adenosine infusion rate of 30 micrograms.kg-1.min-1, whereas the systemic vascular resistance index remained unchanged. Thus, adenosine, administered centrally in anesthetized patients with normal pulmonary vascular resistances, selectively lower pulmonary vascular resistance. The basis for this selective effect is the substantial extraction of adenosine during passage through the pulmonary vascular bed.

Nisoldipine inhibits vasoconstrictor responses in the cat pulmonary vascular bed

1989 ◽  
Vol 66 (6) ◽  
pp. 2885-2890 ◽  
Author(s):  
P. J. Kadowitz ◽  
H. L. Lippton ◽  
J. A. Bellan ◽  
A. L. Hyman
Keyword(s):  
Arterial Pressure ◽  
Vascular Resistance ◽  
Blocking Agent ◽  
Systemic Arterial Pressure ◽  
Calcium Entry ◽  
Bay K 8644 ◽  
Vascular Bed ◽  
Adrenoceptor Agonists ◽  
Thromboxane Receptors ◽  
Pulmonary Vascular Bed

The influence of nisoldipine, a dihydropyridine calcium entry antagonist, on vascular resistance and vasoconstrictor responses was investigated in the feline pulmonary vascular bed under conditions of controlled blood flow. The calcium channel blocking agent caused a small reduction in lobar vascular resistance and blocked pulmonary vasoconstrictor responses to BAY K 8644, an agent which promotes calcium entry. The calcium entry blocking agent also reduced pulmonary vasoconstrictor responses to methoxamine and to BHT 933, alpha 1- and alpha 2-adrenoceptor agonists, and to U 46619, an agent which mimics the actions of thromboxane A2. Although there was a marked difference in vasoconstrictor potency in the pulmonary vascular bed, responses to the thromboxane mimic and to the alpha 1- and alpha 2-adrenoceptor agonists were reduced by approximately the same extent. The increases in systemic arterial pressure in response to BAY K 8644, methoxamine, and BHT 933 were also reduced by nisoldipine, and the calcium entry antagonist reduced systemic arterial pressure and systemic vascular resistance. The results of the present study suggest that an extracellular source of calcium is required for the maintenance of vascular tone and for the expression of vasoconstrictor responses, resulting from activation of alpha 1- and postjunctional alpha 2-adrenoceptors and thromboxane receptors in the feline pulmonary vascular bed.

Analysis of responses to sympathetic nerve stimulation in the feline pulmonary vascular bed

1989 ◽  
Vol 67 (1) ◽  
pp. 371-376 ◽  
Author(s):  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Vascular Resistance ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Receptor Subtypes ◽  
Sympathetic Nerve Stimulation ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Vascular Bed ◽  
Beta 2 ◽  
Pulmonary Vascular Bed

The adrenergic receptor subtypes mediating the response to sympathetic nerve stimulation in the pulmonary vascular bed of the cat were investigated under conditions of controlled blood flow and constant left atrial pressure. The increase in lobar vascular resistance in response to sympathetic nerve stimulation was reduced by prazosin and to a lesser extent by yohimbine, the respective alpha 1- and alpha 2-adrenoceptor antagonists. Moreover, in animals pretreated with a beta-adrenoceptor antagonist to prevent an interaction between alpha- and beta 2-adrenoceptors, responses to nerve stimulation were reduced by prazosin, but yohimbine had no significant effect. On the other hand, in animals pretreated with a beta-adrenoceptor antagonist, yohimbine had an inhibitory effect on responses to tyramine and to norepinephrine. Propranolol had no significant effect on the response to nerve stimulation, whereas ICI 118551, a selective beta 2-adrenoceptor antagonist, enhanced responses to nerve stimulation and injected norepinephrine. The present data suggest that neuronally released norepinephrine increases pulmonary vascular resistance in the cat by acting mainly on alpha 1-adrenoceptors and to a lesser extent on postjunctional alpha 2-adrenoceptors but that this effect is counteracted by an action on presynaptic alpha 2-receptors. The present studies also suggest that neuronally released norepinephrine acts on beta 2-adrenoceptors and that the response to sympathetic nerve stimulation represents the net effect of the adrenergic transmitter on alpha 1-, alpha 2-, and beta 2-adrenoceptors in the pulmonary vascular bed.

Adrenergic mechanisms in canine intralobar pulmonary arteries and veins

1981 ◽  
Vol 240 (2) ◽  
pp. H274-H285 ◽  
Author(s):  
S. Greenberg ◽  
P. J. Kadowitz ◽  
A. Hyman ◽  
F. A. Curron
Keyword(s):  
Adrenergic Receptor ◽  
Pulmonary Arteries ◽  
Blocking Agent ◽  
Adrenergic Innervation ◽  
Pulmonary Vasculature ◽  
Contractile Responses ◽  
Blocking Agents ◽  
Alpha Receptors ◽  
System 2 ◽  
Arteries And Veins

The responses of canine intralobar pulmonary arteries (IPA) and veins (IPV) to transmural nerve stimulation (TNS), and exogenously administered norepinephrine (NE) were studied to evaluate the alpha-adrenergic neuroeffector system in the canine pulmonary vasculature. IPA and IPV elicited contractions in response to both NE (10(-10) to 10(-5) M) and TNS (0.5-32 Hz, 2 ms duration and delay). The equilibrium (steady state) contractile responses of IPA and IPV to TNS were abolished with the adrenergic neuronal blocking agents guanethidine and bretylium and the depolarization blocking agent tetrodotoxin in concentrations which did not affect the responses to NE or KCl. The contractile responses of IPA and IPV to TNS and NE were reduced in a concentration-dependent way, by the alpha-adrenergic receptor-blocking agents phentolamine, tolazoline and clonidine. The contractile responses of IPA and IPV to TNS and NE were enhanced after inhibition of neuronal reuptake of NE (uptake1) with cocaine, as well as after blockade of extraneuronal reuptake of NE (uptake2) with hydrocortisone. Analysis of the equilibrium responses of the IPA and IPV to TNS and NE with an Arunlakshana-Schild plot to define the concentration of alpha 1-receptor antagonists necessary to double the ED50 for TNS and NE (defined as the pA2), demonstrated that the postsynaptic alpha-receptors of IPV differed from that of IPA. These data support the conclusions that IPA and IPV 1) contain a functional adrenergic innervation and neuroeffector system, 2) contract in response to both TNS and NE, 3) demonstrate the presence of mechanisms for both uptake1 and uptake2 of NE, and 4) IPV contain postsynaptic alpha-receptors that may differ from each other.

Influence of inhibitors of prostaglandin synthesis on the canine pulmonary vascular bed

1975 ◽  
Vol 229 (4) ◽  
pp. 941-946 ◽  
Author(s):  
PJ Kadowitz ◽  
BM Chapnick ◽  
PD Joiner ◽  
AL Hyman
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Airway Pressure ◽  
Left Atrial ◽  
Prostaglandin Synthesis ◽  
Left Atrial Pressure ◽  
Small Arteries ◽  
Vascular Bed ◽  
Pulmonary Vascular Bed

The effects of two chemically dissimilar inhibitors of prostaglandin (PG) synthesis on vascular resistance and responses to pressor and depressor hormones were evaluated in the canine pulmonary vascular bed. Indomethacin or meclofenamate, 2.5-5 mg/kg iv, increased lobar arterial pressure. Since lobar blood flow was held constant and left atrial pressure did not change, the rise in pressure reflects an increase in vascular resistance. The rise in lobar pressure after indomethacin occurred in the absence of a change in lobar venous or translobar airway pressure. This agent enhanced the response to angiotensin but not to norepinephrine. Meclofenamate decreased responses to both agents. Indomethacin enhanced the dilator response to PGE1 and both indomethacin and meclofenamate increased the response to PGF2alpha. These data indicate that the rise in resistance after indomethacin or meclofenamate was the result of vasoconstriction in vessels upstream to the small veins, presumed to be small arteries. These data are consistent with the hypothesis that under resting conditions synthesis of a dilator prostaglandin may be important for the maintenance of the pulmonary vascular bed in a dilated state. However, results of the present study are not consistent with the postulate that prostaglandins modulate responses to norepinephrine but suggest that indomethacin and meclofenamate interfere with the inactivation of PGF2alpha and PGE1 in the lung.

Distributions of vascular pressure and resistance in the lung

1988 ◽  
Vol 64 (1) ◽  
pp. 274-284 ◽  
Author(s):  
C. A. Dawson ◽  
T. A. Bronikowski ◽  
J. H. Linehan ◽  
D. A. Rickaby
Keyword(s):  
Vascular Resistance ◽  
Local Minimum ◽  
Vascular Volume ◽  
Low Viscosity ◽  
Vascular Bed ◽  
Residual Capacity ◽  
Capillary Bed ◽  
Arteries And Veins ◽  
Intravascular Pressure ◽  
Lung Lobes

The low-viscosity bolus method was used to determine the longitudinal distributions of vascular resistance and intravascular pressure with respect to cumulative vascular volume from the lobar artery to the lobar vein in isolated dog lung lobes near functional residual capacity under zone 3 conditions. We found that the resistance distribution had two modes, a larger one upstream and a smaller one downstream from a local minimum. Over the range of vascular pressures studied the total vascular resistance decreased and the vascular volume increased with increasing vascular pressure. However, the shape of the normalized resistance distribution was independent of vascular pressure. Comparisons of the resistance distributions with the distributions of arterial, capillary, and venous volumes suggest that the modes represent regions of relatively high resistance proximal and distal to the capillary bed. These results are consistent with the concept that within the lobar vascular bed the highest resistance per unit blood volume is in the smallest arteries and veins, as suggested by morphometric data from other sources.

Effect of dihomo-gamma-linolenic acid on the canine pulmonary vascular bed

1978 ◽  
Vol 234 (2) ◽  
pp. H133-H138
Author(s):  
A. L. Hyman ◽  
E. W. Spannhake ◽  
B. M. Chapnick ◽  
D. B. McNamara ◽  
A. A. Mathe ◽  
...  
Keyword(s):  
Linolenic Acid ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arteries ◽  
Transpulmonary Pressure ◽  
Lung Compliance ◽  
Gamma Linolenic Acid ◽  
Vascular Bed ◽  
Vasoconstrictor Response ◽  
Pulmonary Vascular Bed

The effect of dihomo-gamma-linolenic acid (DGLA), the precursor of the monoenoic prostaglandins (PG), F1alpha and E1, on the pulmonary vascular bed of the intact dog was studied under conditions of controlled pulmonary blood flow. DGLA increased pulmonary vascular resistance in a dose-related manner by constricting intrapulmonary veins and upstream segments, presumably pulmonary arteries. Intrapulmonary injection of DGLA also increased transpulmonary injection of DGLA also increased transpulmonary airway pressure, presumably by increasing airway resistance and decreasing lung compliance or both. The vasoconstrictor response, however, was independent of changes in transpulmonary pressure since similar pressor responses were obtained in ventilated and nonventilated lungs. Further, the response was not dependent on factors or elements in whole blood, since the increase in pulmonary vascular resistance occurred during perfusion with saline or dextran and was enhanced in these media. Conversion of DGLA to PGs by a lung cyclo-oxygenase appears to mediate the response, since it was blocked by indomethacin and dose not occur with injection of nonprecursor long-chain fatty acids. These data suggest that the response to DGLA is due to formation of vasoactive products in the monoenoic PG pathway.

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