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Biomedical subjects

A D Kaye

Publications and source records attributed to A D Kaye.

At least 55 records · Page 3Linked to original sources
PubMed1997

Analysis of responses to bradykinin in the rat hindquarters vascular bed.

The mechanism by which bradykinin (BK) decreases vascular resistance was investigated in the hindquarters vascular bed of the rat. Under conditions of controlled blood flow, BK produced dose-related decreases in hindquarters perfusion pressure when injected into the perfusion circuit in doses of 0.1-1.0 pg. Responses to BK were reproducible with respect to time, and HOE-140 (D-Arg, [Hyp3,Thi5,D-Tic7,Oic8] -BK), a kinin B2 receptor antagonist, decreased hindquarters vasodilator responses to the peptide. HOE-140 had no significant effect on responses to vasodilator agents, which act by a variety of pharmacologically distinct mechanisms. Nitric oxide synthase inhibitors N(omega)-nitro-L-arginine methyl ester or N(omega)-nitro-L-arginine benzyl ester did not decrease responses to BK in doses that decreased hindquarters vasodilator responses to acetylcholine. The cyclooxygenase inhibitors meclofenamate and indomethacin had no effect on responses to BK in doses that attenuated vasodilator responses to the prostaglandin precursor, arachidonic acid. Clotrimazole or 5,8,11,14-eicosatetraynoic acid (ETYA), cytochrome P-450 arachidonic acid metabolism inhibitors, in doses that attenuated vasodilator responses to arachidonic acid, had no effect on responses to BK. Glybenclamide or U-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl), K+-ATP channel antagonists, in doses that attenuated responses to lemakalim, had no significant effect on responses to BK. Finally, des-Arg9-BK, a reported kinin B1 receptor agonist, decreased hindquarters perfusion pressure when injected in doses of 3-30 microg, and responses to the B1 agonist were attenuated by HOE-140. The observation that des-Arg9-BK, in high doses, induces modest HOE-140-sensitive responses suggests that kinin B1 receptors are not normally expressed in the hindquarters vascular bed of the rat. The present results indicate that BK dilates the hindquarters vascular bed by a kinin B2 receptor mechanism that is independent of the release of nitric oxide, cyclooxygenase, or P-450 metabolites of arachidonic acid or the activation of K+-ATP channels.

Adenosine Triphosphate↗
PubMed1996

Analysis of responses to pentoxifylline in the pulmonary vascular bed of the cat.

OBJECTIVE: To test the hypothesis that pulmonary vasodilator responses to pentoxifylline are dependent on the synthesis of nitric oxide from L-arginine and are independent of the release of cyclooxygenase products. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Isolated lobar lung preparation, using mongrel cats. INTERVENTIONS: In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, and the effects of a cyclooxygenase blocker, meclofenamate, were investigated on pulmonary arterial responses to pentoxifylline, acetylcholine, and isoproterenol during increased tone conditions induced by the thromboxane A2 mimic, U46619, in the pulmonary vascular bed of the cat. MEASUREMENTS AND MAIN RESULTS: Lobar arterial perfusion pressure, systemic pressure, and left atrial pressure were continuously monitored, electronically averaged, and permanently recorded. Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, NG-L-nitro-L-arginine methyl ester significantly reduced the vasodilator responses to pentoxifylline and to acetylcholine, whereas NG-L-nitro-L-arginine methyl ester had no significant effect on the vasodilator responses to isoproterenol. Vasodilator responses to pentoxifylline and acetylcholine were not significantly changed in the presence of meclofenamate, whereas meclofenamate markedly reduced the vasopressor effects of arachidonic acid. CONCLUSIONS: These data show that pentoxifylline has significant vasodilator activity in the pulmonary vascular bed of the cat. The present data also suggest that responses to pentoxifylline during increased tone conditions may, in part, be mediated by the release of nitric oxide and are independent of the release of cyclooxygenase products.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Analysis of vancomycin in the hindlimb vascular bed of the rat.

Previously, studies have demonstrated that the effects of both a laboratory-produced vancomycin and a clinically available vancomycin were mediated, in part, by activation of both H(1) and H(2) receptors; however, other mechanisms may play a role in the vascular changes associated with vancomycin, since neither H(1) and H(2) receptor blockade has completely abolished the vasodilator responses to vancomycin in any model system. To study the mechanisms of vancomycin interactions in the hindlimb vascular bed of the rat, responses of two types of vancomycin preparations were studied. Vancomycin prepared for either clinical or laboratory use produced an initial short-lived period of vasoconstriction followed by a prolonged period of vasodilation in the hindlimb vascular bed. Responses to both the vancomycins and histamine on systemic arterial vasodilation were significantly decreased after administration of both the H(1)-receptor antagonist diphenhydramine and the H(2)-receptor antagonist famotidine. Verapamil, an L-type calcium channel blocker, significantly reduced the vasopressor responses to clinical vancomycin but not the vasopressor responses to laboratory vancomycin. Enalaprilat, and angiotensin-converting enzyme blocker, significantly reduced the vasodilator responses but not the vasoconstrictor responses of clinical vancomycin and significantly reduced the vasoconstrictor responses but not the vasodilator responses to laboratory vancomycin. Meclofenamate, a cyclo-oxygenase inhibitor, and N(omega)-L-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthetase inhibitor, had no significant effect on the biphasic responses with either vancomycin preparations. Atropine, an anticholinergic-antimuscarinic receptor antagonist, and propranolol, a beta adrenergic blocker, had no significant effect on vancomycin responses. Finally, ondansetron, a serotonin receptor blocker, and HOE 140, a bradykinin receptor blocker, also had no significant effect on vancomycin responses. These data suggest that both vancomycin preparations (clinically available and laboratory prepared) caused biphasic responses that differed from the dose-dependent vasodilation elicited by histamine. Both vancomycin preparations' vasodilator responses appear to be modulated, in part, by a histamine receptor--sensitive mechanism, while vancomycin-induced vasoconstrictor responses appear to be modulated, in part, by angiotensin-converting enzyme and L-type calcium channel--sensitive mechanisms in the rat hindlimb vascular bed. These data also suggest that the vascular responses of vancomycin are preparation dependent.

Journal Article↗
PubMed1996

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

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.

Adrenomedullin↗
PubMed1995

Responses to L-163,491, a nonpeptide angiotensin II mimic, in the pulmonary vascular bed of the cat.

Pulmonary vascular responses to 5,7-dimethyl-2-ethyl-3-[[2'-[butyloxycarbonyl)amino-sulfonyl]-5'-(3-meth oxybenzyl)-[1,1'-biphenyl]-4-yl]methyl]-3H-imidazo[4,5-b]pyridine (L-163,491), a novel nonpeptide angiotensin agonist, and angiotensin IV, the 3-8 amino acid fragment of angiotensin, were compared with responses to angiotensin II. Responses were investigated in the intact-chest cat under conditions of controlled blood flow and intralobar injections of angiotensin II, L-163,491, and angiotensin IV caused dose-related increases in lobar arterial pressure. When comparable in lobar arterial pressure of the three agents were examined, L-163,491 was approximately 3-fold less potent than angiotensin IV and approximately 100-fold less potent than angiotensin II when doses are expressed on a nmol basis. DuP 532, 2-propyl-4-pentafluoroethyl-1-([2'-(1H-tetrazol-5-yl)bipheny l-4]-methyl)imidazole-5-carboxylic acid, an angiotensin II AT1 receptor antagonist, reduced pulmonary vasoconstrictor responses to angiotensin II, angiotensin IV and L-163,491, but did not significantly change pressor responses to serotonin, norepinephrine, or the thromboxane A2 mimic, U46619. PD 123319, an angiotensin II subtype 2 receptor antagonist, did not significantly change pressor responses to L-163,491, angiotensin II, or angiotensin IV. Captopril, the angiotensin-converting enzyme inhibitor, decreased pulmonary vasoconstrictor responses to angiotensin I and enhanced vasodilator responses to bradykinin, but did not significantly change pressor responses to L-163,491. These data show that L-163,491 significant angiotensin AT1 receptor-mediated vasoconstrictor activity in the pulmonary vascular bed of the cat. These data also show the nonpeptide agonist has 3-fold less activity compared to angiotensin IV and is approximately 100-fold less potent than angiotensin II in the feline pulmonary vascular bed.

Angiotensin II↗
PubMed1995

Analysis of responses of allicin, a compound from garlic, in the pulmonary vascular bed of the cat and in the rat.

Allicin, diallyl disulfide-oxide, an active ingredient released from garlic is a systemic vasodilator that acts by an unknown mechanism. In the present experiments, pulmonary vascular responses to allicin (0.1-1.0 mg) were studied in the intact-chest anesthetized cat and in the isolated lung of the rat under constant flow conditions. When baseline tone in the pulmonary vascular bed of the cat was raised with U46619 (11 alpha,9 alpha-epoxymethano-9 alpha,11 beta-dideoxyprostaglandin F2 alpha), intralobar injections of allicin produced dose-related decreases in pulmonary arterial pressure without changing left atrial pressure indicating that allicin had significant vasodilator activity in the pulmonary vascular bed when tone was increased experimentally. Allicin also decreased systemic arterial pressure in a dose-related manner. In terms of relative vasodilator activity in the cat, allicin was 100-fold less potent than sodium nitroprusside and many orders of magnitude less potent than isoproterenol. In the cat, vasodilator responses to allicin were unchanged by methylene blue or N omega-nitro-L-arginine methyl ester. Allicin also significantly diminished the pulmonary pressor response to ventilatory hypoxia in the isolated perfused rat lung. These data show that allicin has significant vasodilator activity in the pulmonary vascular bed of the cat and the rat. The present data suggest that pulmonary vasodilator responses to allicin are independent of the synthesis of endothelial-derived relaxing factor or the activation of soluble guanylate cyclase.

Animals↗
PubMed1995

Responses to a nonpeptide angiotensin receptor agonist, L 163491, in the feline pulmonary vascular bed.

The mechanism by which a novel potent non-peptide angiotensin subtype 1 receptor (AT1) agonist, (5,7-dimethyl-2-ethyl-3-[[2'-[(butyloxycarbonyl) aminosulfonyl]-5'-(3-methoxybenzyl)-[1,1'-biphenyl]-4-yl] methyl]-3H-imidazo [4,5-b] pyridine) (L-163,491), increased pulmonary vascular resistance was investigated in the intact-chest anesthetized cat under conditions of controlled blood flow. Intralobar injections of L-163,491, in doses of 10-300 micrograms i.a., caused dose-related increases in lobar arterial pressure that were partially antagonized by an AT1 receptor antagonist, DuP 532, or by staurosporine, a protein kinase C inhibitor, in doses that antagonized pressor responses to Ang II, but not to the thromboxane A2 mimic, U46619. Responses to L 163491 were not altered by PD 123319, an AT2 receptor antagonist. These data provide support for the hypothesis that vasoconstrictor responses to L 163491 are mediated by the activation of AT1 receptors and the protein kinase C pathway in the pulmonary vascular bed of the intact-chest cat.

Alkaloids↗
PubMed1995

Local anesthesia infiltration as a cause of intraoperative tension pneumothorax in a young healthy woman undergoing breast augmentation with general anesthesia.

Pneumothorax may be a medical emergency. Iatrogenic pneumothorax is more common than all other forms of spontaneous pneumothorax, and surgical procedures involving the breast are a frequent setting for this. A 32-year-old, 60 kg, woman without any significant medical history underwent a bilateral breast augmentation and rhinoplasty. She underwent a routine general endotracheal anesthetic. Prior to surgical incision, the surgeon infiltrated the breast with lidocaine with epinephrine. Six hours into the surgical procedure, the patient developed hemodynamic compromise and was diagnosed with tension pneumothorax, which was treated emergently with a 14-gauge angiocatheter placed intrapleurally. The patient immediately returned to hemodynamic stability. This case report discusses iatrogenic pneumothoraces as well their most likely causes; which in this specific case was the injection of local anesthetic. Suggestions for prevention and treatment of the unusual complication are discussed.

Adult↗
PubMed1995

Analysis of thromboxane receptor-mediated responses in the feline pulmonary vascular bed.

OBJECTIVE: Current evidence suggests that thromboxane plays a role in pathophysiologic processes in the lung. Efforts to find effective, specific therapy to modify these effects have led to the development of a new class of thromboxane receptor blockers. This present investigation examined the selectivity and duration of the inhibitory effects of one of these novel agents in the pulmonary vascular bed of anesthetized cats. DESIGN: Prospective, randomized, controlled study with repeated measures. SETTING: University research laboratory. SUBJECTS: Twenty-nine adult cats obtained from the Tulane University School of Medicine vivarium. INTERVENTIONS: The effects of GR32191, a thromboxane receptor antagonist, were investigated under constant-flow conditions in the intact-chest cat, using a triple-lumen, 6-Fr, balloon perfusion catheter that was placed by means of fluoroscopic guidance. Data were analyzed using a paired or unpaired t-test or analysis of variance. A p < .05 was considered statistically significant. MEASUREMENTS AND MAIN RESULTS: Aortic, left atrial, and left lobar arterial pressures were measured. After administration of GR32191 (0.25 and 1.0 mg/kg iv), pulmonary vasoconstrictor responses to U46619, a thromboxane mimic, were significantly decreased. Blockade was overcome with higher doses of the thromboxane mimic. GR32191 was without significant effect on the responses to prostaglandin (PG) D2, PGF2 alpha, serotonin, the calcium-channel agonist BAY K8644, or norepinephrine. Additionally, GR32191 did not alter baseline vascular pressures. Responses to U46619 returned to 50% of control value 90 mins after administration of 0.25 mg/kg of U46619. Responses to GR32191 returned to 50% of control value 180 mins after administration of 1.0 mg/kg of GR32191. These data suggest that GR32191 selectively blocks thromboxane A2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed of the cat. CONCLUSIONS: These results are consistent with the hypothesis that discrete thromboxane A2 receptors, unrelated to receptors activated by PGF2 alpha or PGD2, are present in the feline pulmonary vascular bed. Specific thromboxane receptor antagonists, such as GR32191, could be useful therapeutic agents in the treatment of pulmonary hypertensive and thromboembolic disorders.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Analysis of responses to ANG IV: effects of PD-123319 and DuP-753 in the pulmonary circulation of the rat.

Pulmonary vasoconstrictor responses to angiotensin (ANG) IV, the 3-8 amino acid fragment of ANG II, were compared with responses to ANG I, ANG II, and ANG III and to other vasoactive peptides in the isolated blood perfused rat lung. In terms of relative activity, ANG IV was similar in potency to bradykinin and serotonin but was approximately 100-fold less potent than ANG I, ANG II, and ANG III. PD-123319, an AT2-receptor antagonist, enhanced pressor responses to the four angiotensin peptides and to bradykinin but did not significantly change the pressor response to serotonin or to ventilatory hypoxia. DuP-753, an AT1-receptor antagonist, significantly decreased pressor responses to the four angiotensin peptides and enhanced the pressor responses to bradykinin but not to serotonin. Captopril and enalaprilat increased the pressor response to ANG IV. Meclofenamate and N omega-nitro-L-arginine methyl ester shifted the dose-response curve for ANG IV to the left in a manner similar to that observed with ANG II and ANG III. These data show that ANG IV has significant vasoconstrictor activity and suggest that responses are mediated by the activation of AT1 receptors and that vasopressor responses of the angiotensin peptides may be modulated by activation of AT2 receptors. These results also suggest that responses to ANG IV are modulated by the release of vasodilator prostaglandins and nitric oxide and that AT2 receptors have little, if any, role in mediating or modulating the pressor response to ventilatory hypoxia.

Angiotensin II↗
PubMed1995

Influence of protein kinase C inhibitors on vasoconstrictor responses in the pulmonary vascular bed of cat and rat.

The effects of staurosporine and calphostin C, two different protein kinase C (PKC) inhibitors, on pressor responses were studied in the pulmonary vascular bed of the intact chest anesthetized cat and the isolated rat lung. Under conditions of constant lobar blood flow in the cat, injections of the angiotensin peptides, norepinephrine (NE), serotonin, and U-46619 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure and responses were reproducible with respect to time. Infusion of staurosporine into the perfused lobar artery at 1-2 micrograms/kg for 10 min reduced the pressor response to the angiotensin peptides and to NE; however, staurosporine did not alter pressor responses to serotonin or to the thromboxane mimic U-46619. In a separate series of experiments, the effects of calphostin C were investigated and infusion of the PKC inhibitor into the perfused lobar artery at 1-5 micrograms/kg for 10 min also reduced pressor responses to the angiotensin peptides and to NE and did not alter pressor responses to serotonin or to U-46619. In the isolated rat lung, the inhibitory effects of staurosporine on pulmonary pressor responses were investigated and injections of angiotensin II, NE, and serotonin produced dose-related increases in pulmonary arterial perfusion pressure that were decreased after administration of 20 micrograms ia of the PKC inhibitor staurosporine. (ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Influence of PLC and MLCK inhibitors and the role of L-calcium channels in the cat 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)

Alkaloids↗
PubMed1995

Analysis of aprotinin on the mean arterial pressure, carotid artery blood flow, and hindlimb vascular resistance in the live rat, and pulmonary vascular resistance in the isolated perfused rat lung.

The effects of aprotinin on mean arterial pressure, carotid artery blood flow, pulmonary vascular resistance, and systemic vascular resistance have not been well documented. Therefore, the responses of aprotinin on the mean arterial pressure, carotid artery blood flow and the changes in pulmonary and hindlimb vascular resistances were investigated in the rat using ultrasonic flow probe analysis, and in two isolated vascular bed preparations. In studies on cardiac output using ultrasonic flow analysis, injections of aprotinin, in doses of 70-7000 KIU intravenously (iv), resulted in no changes in carotid artery ultrasonic flow, suggesting no changes in cardiac output. In isolated blood-perfused lung studies under conditions of controlled pulmonary blood flow, aprotinin, in doses of 7-7000 KIU intra-arterially (ia), caused no significant changes in pulmonary arterial perfusion pressure. Aprotinin, in doses of 7-240 KIU, was injected iv into the hindquarters perfusion circuit, and hindquarters arterial perfusion pressure did not change. Additionally, in the hindquarters perfusion preparation, aprotinin, in doses of 70-7000 KIU, ia resulted in no changes in mean arterial pressure. The present data demonstrate aprotinin has no significant response in MAP, carotid artery blood flow, pulmonary vascular resistance, or hindlimb vascular resistance in the rat.

Animals↗
PubMed1995

Analysis of responses to vancomycin in carotid blood flow in the male rat.

Vancomycin is known to cause vasodilation, and hypotension secondary to histamine release. We studied the actions of two forms of vancomycin, a clinically available preparation, clinical vancomycin, and a research grade preparation, laboratory vancomycin, in the presence of an H1 receptor blockade and during H2 receptor blockade with Doppler flow probe analysis of carotid artery flow rate. Clinical vancomycin, laboratory vancomycin, and histamine, increased the mean carotid artery blood flow from baseline in a dose-dependent manner. Diphenhydramine, H1 receptor antagonist, attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin and for each dose of histamine. Famotidine, H2 receptor antagonist, significantly attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin, the two higher doses of laboratory vancomycin, and with each dose of histamine. Both diphenhydramine and famotidine attenuated the increase of mean carotid artery blood flow with clinical vancomycin, laboratory vancomycin, and histamine. These data suggest that the change in carotid flow produced by vancomycin, is dependent, in part, on either H1 or H2 receptor activation.

Animals↗
PubMed1994

Influence of N omega-nitro-L-arginine methyl ester, LY83583, glybenclamide and L158809 on pulmonary circulation.

The effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase; 6-anilino-5,8-quinolinedione (LY83583), an inhibitor of soluble guanylate cyclase; glybenclamide, a ATP-sensitive K+ channel blocking agent; and 5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl)-[1,1']-biphenyl-4- yl]methyl]-3H-imidazo[4,5-b]pyridine (L158809), an angiotensin II type I receptor antagonist, on the response to ventilatory hypoxia were investigated in the isolated blood-perfused rat lung. Under conditions of controlled pulmonary blood flow, and constant left atrial pressure, injections of glybenclamide into the pulmonary arterial perfusion circuit significantly increased baseline pulmonary arterial perfusion pressure, whereas administration of N omega-nitro-L-arginine methyl ester produced smaller increases in baseline tone. Ventilatory hypoxia (3% O2-5% CO2-92% N2) significantly increased pulmonary arterial perfusion pressure and the response was reproducible with respect to time. Following administration of N omega-nitro-L-arginine methyl ester or LY83583, the response to hypoxia was significantly increased, whereas the response to hypoxia was not changed by glybenclamide or atropine. N omega-Nitro-L-arginine methyl ester also significantly enhanced pressor responses to angiotensin II, but had no effect on the pressor response to serotonin. When pulmonary vascular tone was increased with hypoxia, vasodilator responses to acetylcholine were inhibited by N omega-nitro-L-arginine methyl ester and vasodilator responses to levcromakalim were reduced by glybenclamide. In addition, L158809 did not alter the pressor response to hypoxia, whereas responses to angiotensin II were reduced in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoquinolines↗
PubMed1994

L-NAME modulates responses to adrenomedullin in the hindquarters vascular bed of the rat.

Responses to synthetic human adrenomedullin (ADM), a novel hypotensive peptide recently discovered in human pheochromocytoma cells, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled hindquarters blood flow, intraarterial injections of ADM (0.01-0.3 nmol) and of CGRP (0.03-0.3 nmol) caused dose-related decreases in hindquarters perfusion pressure and decreases in systemic arterial pressure. Following administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), hindquarters vasodilator and systemic depressor responses to ADM were significantly decreased, whereas L-NAME did not significantly decrease the vasodilator response to CGRP in either the hindquarters or systemic vascular beds. Following administration of the cyclooxygenase inhibitor, meclofenamate, vasodilator responses to ADM and to CGRP were not significantly decreased. When the relative vasodilator activity of the two peptides was compared on a nmol basis, responses to ADM were similar to responses with CGRP in the hindquarters vascular bed, whereas ADM was 30-100 fold less potent than CGRP in decreasing systemic arterial pressure. The present data demonstrate that ADM has significant vasodilator activity in the hindquarters vascular bed of the rat, that hindquarters vasodilator and systemic vasodepressor responses to ADM, but not to CGRP, are dependent upon the release of nitric oxide from the endothelium.

Adrenomedullin↗
PubMed1994

Computed tomographic evaluation of maximal diaphragmatic crural thickness.

The purpose of this study is to determine the range of maximal diaphragmatic crural thickness during different phases of respiration and to correlate crural thickness with age and gender. Prospective evaluation of computed tomographic (CT) scans of 200 patients without juxtacrural abnormalities was performed. Maximal short-axis crural thickness measurements were determined in all patients. Measurements were obtained at full inspiration during chest CT (n = 60), full expiration during abdominal CT (n = 89), and unknown phase of respiration during dynamic CT scans (n = 51). Maximal crural thickness measurements were analyzed by side, age, and gender. The right crus was thicker than the left crus in 91% of patients. The range of maximal crural thickness remained fairly constant from the second to the eighth decades of life. The range of maximal crural thickness was 1.8-18.8 mm in men and 1.8-21.1 mm in women. Maximal crural thickness does not significantly vary with age and gender for specific phase of respiration.

Adult↗