Enhancement of alpha- and beta-adrenoceptor responses by elevations in vascular tone in pulmonary circulation

1986 ◽  
Vol 250 (6) ◽  
pp. H1109-H1116 ◽  
Author(s):  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Vascular Tone ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Steady Level ◽  
Adrenoceptor Agonists ◽  
Beta 2 ◽  
Resting Tone ◽  
Pulmonary Vascular Bed

The influence of increases in vascular tone on responses to selective alpha 1- and alpha 2-adrenoceptor agonists, norepinephrine, epinephrine, and isoproterenol was investigated in the feline pulmonary vascular bed. Under resting tone conditions with constant pulmonary blood flow and left atrial pressure, intralobar injections of the alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, and the alpha 2-adrenoceptor agonists, UK 14304 and B-HT 933, increased lobar arterial pressure. When pulmonary vascular resistance was raised to a high steady level, vasoconstrictor responses to the alpha 2-adrenoceptor agonists were markedly increased, responses to methoxamine were increased to a lesser extent, and pressor responses to phenylephrine and epinephrine were reversed. These vasodilator responses to phenylephrine and epinephrine at elevated vascular tone were blocked by propranolol. Moreover, after beta-adrenoceptor blockade, vasoconstrictor responses to phenylephrine, epinephrine, and norepinephrine were also greater at elevated tone than at resting tone. Vasodilator responses to the beta-adrenoceptor stimulant, isoproterenol, were enhanced at higher levels of vasoconstrictor tone and were blocked by propranolol and by albuterol, a selective beta 2-adrenoceptor antagonist. The enhanced vasoconstrictor responses to the alpha 2-adrenoceptor agonists were selectively blocked by yohimbine, whereas the enhanced responses to the alpha 1-adrenoceptor agonists and, for the most part, the vasoconstrictor responses to norepinephrine and epinephrine, were blocked by prazosin. The present data support the hypothesis that postjunctional alpha 1- and alpha 2-adrenoceptors mediating vasoconstriction and beta 2-adrenoceptors mediating vasodilation are present in the feline pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of tone on responses to acetylcholine in the rabbit pulmonary vascular bed

1989 ◽  
Vol 67 (4) ◽  
pp. 1388-1394 ◽  
Author(s):  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Arterial Pressure ◽  
High Tone ◽  
Biphasic Response ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Steady Level ◽  
Pressor Activity ◽  
Resting Tone ◽  
Higher Doses ◽  
Pulmonary Vascular Bed

Pulmonary vascular responses to acetylcholine were compared under resting and high tone conditions of the intact-chest rabbit. Under resting tone conditions, intralobar injections of acetylcholine increased lobar arterial pressure in a dose-related manner. The pressor responses to acetylcholine under resting conditions were blocked by meclofenamate, indomethacin, atropine, and pirenzepine. When lobar vascular resistance was raised to a high steady level, low doses of acetylcholine decreased lobar arterial pressure, whereas higher doses elicited a biphasic response with the pressor component predominating at the highest dose studied. Under high tone conditions, only the pressor component of the response was blocked by meclofenamate or indomethacin, whereas pressor and depressor responses were blocked by atropine or the 600-micrograms/kg iv dose of pirenzepine. Pressor responses to acetylcholine under resting and high tone conditions were blocked by pirenzepine (50 micrograms/kg iv), whereas gallamine had no effect on responses to acetylcholine. The 50-micrograms/kg iv dose of pirenzepine had no effect on depressor responses or the depressor component of the response to acetylcholine. The present data support the concept that acetylcholine has significant cyclooxygenase-dependent pressor activity in the rabbit pulmonary vascular bed and suggest that this response is mediated by a muscarinic M1-type receptor. These data also show that, under high tone conditions, a vasodilator response or a vasodilator component of a biphasic response is unmasked. This response is not dependent on the release of cyclooxygenase products and is mediated by a muscarinic receptor that is neither of the M1- nor the M2-type.

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.

Evidence for existence of postjunctional alpha 1- and alpha 2-adrenoceptors in cat pulmonary vascular bed

1985 ◽  
Vol 249 (4) ◽  
pp. H891-H898
Author(s):  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Adrenergic Nerve ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Vascular Bed ◽  
Alpha Adrenoceptor Agonists ◽  
Adrenoceptor Blocker ◽  
Adrenoceptor Agonists ◽  
Uk 14,304 ◽  
6 Hydroxydopamine ◽  
Pulmonary Vascular Bed

The subtypes of postjunctional alpha-adrenoceptors in the feline pulmonary vascular bed were studied using selective alpha-adrenoceptor agonists and antagonists. Under conditions of controlled pulmonary blood flow and constant left atrial pressure, intralobar injections of the alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, and the alpha 2-adrenoceptor agonists, UK 14,304 and BHT 933, increased lobar arterial pressure in a dose-related manner. Prazosin, an alpha 1-adrenoceptor antagonist, reduced responses to phenylephrine and methoxamine to a greater extent than responses to UK 14,304 and BHT 933. Yohimbine, an alpha 2-adrenoceptor blocker, decreased responses to UK 14,304 and BHT 933 without altering responses to phenylephrine or methoxamine. The same pattern of blockade was observed in animals pretreated with 6-hydroxydopamine, an agent that destroys the integrity of adrenergic nerve terminals. However, in propranolol-treated animals, prazosin antagonized responses to phenylephrine and methoxamine without altering responses to UK 14,304 or BHT 933, and the selectivity of the blocking effects of yohimbine were preserved. Responses to intralobar injections of norepinephrine were markedly decreased by prazosin, whereas yohimbine had only a small effect. These data suggest the presence of both postjunctional alpha 1- and alpha 2-adrenoceptors mediating vasoconstriction in the pulmonary vascular bed. These results also indicate that the vasoconstrictor responses to injected norepinephrine in the cat pulmonary vascular bed are due mainly to activation of alpha 1-adrenoceptors.

N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin

1991 ◽  
Vol 71 (5) ◽  
pp. 2026-2031 ◽  
Author(s):  
T. J. McMahon ◽  
J. S. Hood ◽  
J. A. Bellan ◽  
P. J. Kadowitz
Keyword(s):  
Methyl Ester ◽  
Left Atrial ◽  
Vascular Tone ◽  
Control Period ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Vascular Bed ◽  
Pulmonary Vasodilator ◽  
Pressor Responses ◽  
Pulmonary Vascular Bed

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was elevated with U-46619, intralobar injections of acetylcholine, bradykinin, sodium nitroprusside, isoproterenol, prostaglandin E1 (PGE1), lemakalim, and 8-bromo-guanosine 3′,5′-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intravenous administration of L-NAME elevated lobar arterial and systemic arterial pressures without altering left atrial pressure. When U-46619 was infused after L-NAME to raise lobar arterial pressure to levels similar to those attained during the control period, vasodilator responses to acetylcholine and bradykinin were reduced significantly, whereas responses to PGE1, lemakalim, and 8-bromo-cGMP were not altered, and responses to nitroprusside were increased. There was a small effect on the response to the highest dose of isoproterenol, and pressor responses to BAY K 8644 and angiotensin II were not altered. These results are consistent with the hypothesis that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine and that EDRF production may have a role in the regulation of tone and in the mediation of responses to acetylcholine and bradykinin in the pulmonary vascular bed of the cat.

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.

Beta adrenoceptors mediate the catecholamine-induced stimulation of oxytocin secretion from cultured bovine granulosa cells

1991 ◽  
Vol 3 (6) ◽  
pp. 715 ◽  
Author(s):  
MR Luck ◽  
M Munker
Keyword(s):  
Granulosa Cells ◽  
Receptor Subtype ◽  
Alpha Adrenoceptors ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Ici 118,551 ◽  
Beta 2 ◽  
Term Response

Bovine granulosa cells were treated in culture with alpha- and beta-adrenoceptor ligands to determine the receptor subtype mediating their response to catecholamines. The secretion of oxytocin by granulosa cells in serum-free medium was measured on the fourth day of culture (during the period of acquisition of a luteal phenotype). Cultures were performed in the presence of 0.5 mM ascorbic acid, which increased hormone output and potentiated the response to catecholamines. The effects of adrenaline and noradrenaline on oxytocin secretion were concentration-dependent; maximum stimulation was over 700% with adrenalin (EC50 92 nM) and 500% with noradrenaline (EC50 87 nM). The response to noradrenaline (10(-6) M) and adrenaline (10(-6) M) could be blocked by propranolol but not by phentolamine, suggesting that beta- rather than alpha-adrenoceptors were involved. Blockade by metoprolol and practolol (beta 1-adrenoceptor antagonists) was poor and dobutamine (beta 1-agonist) was weakly stimulatory. A concentration-dependent stimulatory response (EC50 200 nM) was obtained with salbutamol (beta 2-adrenoceptor agonist) and stimulation by adrenaline or salbutamol could be blocked by a selective beta 2-adrenoceptor antagonist (ICI 118,551). It is concluded that, during luteinization, the long-term response of bovine granulosa cells to stimulation induced by catecholamines is mediated through beta- rather than alpha-adrenoceptors. Although the beta 2-subtype is probably involved, the similar potencies of adrenaline and noradrenaline are uncharacteristic of beta 2-adrenoceptors and may be peculiar to the long-term response shown by these cells.

Tone-dependent responses to acetylcholine in the feline pulmonary vascular bed

1988 ◽  
Vol 64 (5) ◽  
pp. 2002-2009 ◽  
Author(s):  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Arterial Pressure ◽  
Base Line ◽  
High Tone ◽  
Vascular Responses ◽  
Vascular Bed ◽  
Vasoconstrictor Response ◽  
Steady Level ◽  
Low Tone ◽  
Type Receptor ◽  
Pulmonary Vascular Bed

The effects of an increase in base-line tone on pulmonary vascular responses to acetylcholine were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure, intralobar injections of acetylcholine under low-tone base-line conditions increased lobar arterial pressure in a dose-related manner. When tone was increased moderately by alveolar hypoxia, acetylcholine elicited dose-dependent decreases in lobar arterial pressure, and at the highest dose studied, acetylcholine produced a biphasic response. When tone was raised to a high steady level with the prostaglandin analogue, U46619, acetylcholine elicited marked dose-related decreases in lobar arterial pressure. Atropine blocked both vasoconstrictor responses at low tone and vasodilator responses at high tone, whereas meclofenamate and BW 755C had no effect on responses to acetylcholine at low or high tone. The vasoconstrictor response at low tone was blocked by pirenzepine (20 and 50 micrograms/kg iv) but not gallamine (10 mg/kg iv). The vasodilator response at high tone was not blocked by pirenzepine (50 micrograms/kg iv) or gallamine or pancuronium (10 mg/kg iv). The present data support the concept that pulmonary vascular responses to acetylcholine are tone dependent and suggest that the vasoconstrictor response under low-tone conditions is mediated by a high-affinity muscarinic (M1)-type receptor. These data also suggest that vasodilator responses under high-tone conditions are mediated by muscarinic receptors that are neither M1 nor M2 low-affinity muscarinic-type receptor and that responses to acetylcholine are not dependent on the release of cyclooxygenase or lipoxygenase products.

Influence of PLC and MLCK inhibitors and the role of L-calcium channels in the cat pulmonary vascular bed

1995 ◽  
Vol 269 (4) ◽  
pp. L507-L513 ◽  
Author(s):  
A. D. Kaye ◽  
B. D. Nossaman ◽  
I. N. Ibrahim ◽  
P. J. Kadowitz
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Kinase Inhibitor ◽  
Bay K 8644 ◽  
Ang Ii ◽  
Arterial Perfusion ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Pulmonary Vascular Bed

The effects of U-73122, a phospholipase C (PLC) inhibitor, on pressor responses to angiotensin II (ANG II), norepinephrine (NE), serotonin (5-HT), BAY K 8644, and the thromboxane A2 (TxA2) mimic, U-46619, were studied in the pulmonary vascular bed of the intact-chest cat. Under conditions of constant lobar blood flow, injections of ANG II, NE, 5-HT, U-46619, and the calcium channel opener, BAY K 8644, into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure, which were reproducible with respect to time. Infusion of U-73122, a PLC inhibitor, into the perfused lobar artery at 10–100 micrograms/kg for 10 min significantly reduced responses to ANG II, serotonin, and NE; however, U-73122 did not alter responses to BAY K 8644 or to U-46619. In a separate series of animals, the effects of the myosin light chain kinase inhibitor, KT-5926, were investigated, and after infusion of KT-5926 into the perfused lobar artery at 1–2 micrograms/kg for 10 min, responses to ANG II, NE, 5-HT, BAY K 8644, and U-46619 were reduced significantly. In a final series of experiments, the effects of the L-type calcium channel blocker, nicardipine, were investigated, and infusion of the L-type calcium channel blocker into the perfused lobar artery at 0.5-1 microgram/kg for 10 min reduced responses to ANG II, BAY K 8644, and NE. However, nicardipine did not alter pressor responses to 5-HT or the TxA2 mimic, U-46619.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Catecholamines modulate podocyte function.

1998 ◽  
Vol 9 (3) ◽  
pp. 335-345 ◽  
Author(s):  
T B Huber ◽  
J Gloy ◽  
A Henger ◽  
P Schollmeyer ◽  
R Greger ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Patch Clamp Technique ◽  
Extracellular Solution ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists ◽  
Beta 2 ◽  
Cl Conductance ◽  
Stimulation Of ◽  
Ion Conductances

The aim of this study was to investigate the influence of adrenoceptor agonists on the intracellular calcium activity ([Ca2+]i), membrane voltage (Vm), and ion conductances (Gm) in differentiated mouse podocytes. [Ca2+]i was measured by the Fura-2 fluorescence method in single podocytes. Noradrenaline and the alpha 1-adrenoceptor agonist phenylephrine induced a reversible and concentration-dependent biphasic increase of [Ca2+]i in podocytes (EC50 approximately 0.1 microM for peak and plateau), whereas the alpha 2-adrenoceptor agonist UK 14.304 did not influence [Ca2+]i. The [Ca2+]i response induced by noradrenaline was completely inhibited by the alpha 1-adrenoceptor antagonist prazosin (10 nM). In a solution with a high extracellular K+ (72.5 mM), [Ca2+]i was unchanged and the [Ca2+]i increase induced by noradrenaline was not inhibited by the L-type Ca2+ channel blocker nicardipine (1 microM). Vm and Gm were examined with the patch-clamp technique in the slow whole-cell configuration. Isoproterenol, phenylephrine, and noradrenaline depolarized podocytes and increased Gm. The order of potency for the adrenoceptor agonists was isoproterenol (EC50 approximately 1 nM) > noradrenaline (EC50 approximately 0.3 microM) > phenylephrine (EC50 approximately 0.5 microM). The beta 2-adrenoceptor antagonist ICI 118.551 (5 to 100 nM) inhibited the effect of isoproterenol on Vm. Stimulation of adenylate cyclase by forskolin mimicked the effect of isoproterenol on Vm and Gm (EC50 approximately 40 nM). Isoproterenol induced a time- and concentration-dependent increase of cAMP in podocytes. The effect of isoproterenol was unchanged in the absence of Na+ or in an extracellular solution with a reduced Ca2+ concentration, whereas it was significantly increased in an extracellular solution with a reduced Cl- concentration (from 145 to 32 mM). The data indicate that adrenoceptor agonists regulate podocyte function: They increase [Ca2+]i via an alpha 1-adrenoceptor and induce a depolarization via a beta 2-adrenoceptor. The depolarization is probably due to an opening of a cAMP-dependent Cl- conductance.

Influence of Zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed

1993 ◽  
Vol 74 (4) ◽  
pp. 1704-1711 ◽  
Author(s):  
T. J. McMahon ◽  
L. J. Ignarro ◽  
P. J. Kadowitz
Keyword(s):  
Arterial Pressure ◽  
Left Atrial ◽  
Vascular Tone ◽  
Vagal Stimulation ◽  
Phosphodiesterase Inhibitor ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Synthesis Inhibitor ◽  
Vascular Bed ◽  
Pulmonary Vascular Bed

The influence of Zaprinast (M&B 22948), a guanosine 3′,5′-cyclic monophosphate (cGMP)-specific phosphodiesterase inhibitor, was investigated in the pulmonary vascular bed of the cat under conditions of controlled blood flow and constant left atrial pressure. Under baseline conditions, injections of Zaprinast into the perfused lobar artery produced small decreases in lobar arterial pressure without altering systemic arterial or left atrial pressure. When tone was increased with U-46619, Zaprinast caused larger dose-dependent decreases in lobar arterial pressure without altering left atrial pressure. The decreases in lobar arterial pressure were reduced significantly by treatment with the nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the guanylate cyclase inhibitor methylene blue. Under elevated tone conditions, efferent vagal stimulation and intralobar injections of acetylcholine, substance P, NO solution, and the S-nitrosothiols [S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-L-cysteine (CysNO)] decreased lobar arterial pressure in a frequency-dependent and dose-related manner. After treatment with Zaprinast, the decreases in lobar arterial pressure in response to efferent vagal stimulation, the endothelium-dependent vasodilators, and the nitrovasodilators were not changed, whereas the duration of the vasodilator responses as measured by the half times was increased significantly. Vasodilator responses to adenosine, albuterol, and pinacidil were not altered by Zaprinast. These data suggest that cGMP hydrolysis in the lung is rapid and that endothelium-derived NO is important in stimulating basal cGMP production and in regulating vascular tone.(ABSTRACT TRUNCATED AT 250 WORDS)

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