Biomedical subjects

J S Hood

Publications and source records attributed to J S Hood.

16 recordsLinked to original sources

PubMed1993

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

Pulmonary vascular responses to serotonin (5-hydroxytryptamine; 5-HT) were investigated in the intact-chest cat under constant-flow conditions. Injections of 5-HT into the perfused lobar artery in doses of 1-30 micrograms caused dose-related increases in lobar arterial pressure and, at doses of 3-30 micrograms, decreases in systemic arterial pressure. Left atrial pressure was not changed, and responses to 5-HT were not altered by a thromboxane receptor blocking agent. Responses to 5-HT were blocked by ketanserin in doses that did not alter responses to agonists that increase pulmonary vascular resistance by various mechanisms. The ketanserin-induced blockade was not surmountable and at a dose of 0.5 mg/kg iv persisted for > 4 h. Prazosin and yohimbine, selective alpha 1- and alpha 2-adrenoceptor antagonists, were without effect on the pressor response to 5-HT, and ketanserin did not reduce responses to norepinephrine or the alpha 1-agonists, phenylephrine and methoxamine. 5-HT and the thromboxane mimic, U-46619, produced large increases in pulmonary vascular resistance; however, U-46619 was 300 times more potent than 5-HT. 5-HT increased lobar arterial pressure when the lung was perfused with dextran, and increases in lobar arterial pressure in response to 5-HT were not diminished when lobar ventilation was interrupted but were enhanced by N omega-nitro-L-arginine methyl ester and to a small extent by meclofenamate. The present data suggest that increases in pulmonary vascular resistance in the cat in response to 5-HT are due to activation of an S2 receptor in undefined "resistance vessel elements." These data suggest that pulmonary vasoconstrictor responses to 5-HT may be modulated to a small extent by release of a vasodilator prostaglandin and endothelium-derived nitric oxide but are not dependent on activation of thromboxane receptors, changes in bronchomotor tone, and interaction with alpha 1-receptors or with formed elements in blood.

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

PubMed1992

Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban.

The effects of sulotroban (BM13.177; SK & F 95587), a thromboxane (TX) A2/endoperoxide (PGH2) receptor blocking agent on responses to the TXA2/PGH2 mimics, U46619 and U44069, were investigated in the pulmonary vascular bed of the intact-chest cat under constant flow conditions. Injections of U46619 and U44069 directly into the perfused lobar artery caused dose-related increases in lobar arterial pressure without altering left atrial pressure. Following administration of sulotroban in a dose of 5 mg/kg i.v., dose-response curves for U46619 and U44069 were shifted to the right in a parallel manner. The duration of the blocking effect of sulotroban was investigated, and responses to U46619 returned to approximately 50% of control in 120 min and were not significantly different from control 240 min after administration of the receptor antagonist. Sulotroban was without significant effect on responses to prostaglandin (PG) D2 or F2 alpha or serotonin, histamine, norepinephrine, angiotensin II or BAY K8644, an agent which enhances calcium entry. Sulotroban was without effect on responses to endothelin (ET)-1, sarafotoxin (S) 6a or S6c and platelet-activating factor (PAF). Sulotroban did not alter baseline vascular pressures in the cat and responses to the PG and TXA2/PGH2 precursor, arachidonic acid, were reduced. The present data show that sulotroban selectively blocks TXA2/PGH2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1992

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

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.

Animals↗

PubMed1992

Characterization of thromboxane receptor blocking effects of SQ 29548 in the feline pulmonary vascular bed.

The effects of SQ 29548, a thromboxane (Tx) A2 receptor blocking agent, on responses to the TxA2 mimic U46619 were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 29548 in doses of 0.25-1 mg/kg iv reduced vasoconstrictor responses to U-46619; however, responses to prostaglandins (PG) F2 alpha and D2 and to serotonin were also decreased. After administration of SQ 29548 in doses of 0.05-0.1 mg/kg iv, responses to U-46619 and U-44069 were reduced significantly, and the dose-response curves for these TxA2 mimics were shifted to the right in a parallel manner at a time when responses to PGF2 alpha and PGD2 were not altered. The low doses of the TxA2 receptor blocking agent significantly reduced responses to the PG and TxA2 precursor arachidonic acid but were without significant effect on vasoconstrictor responses to serotonin; histamine; norepinephrine; angiotensin II; the major PGD2 metabolite 9 alpha,11 beta-PGF2; BAY K 8644, an agent that enhances calcium entry; and endothelin-1. The present data show that at low doses SQ 29548 selectively blocks TxA2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed. These data suggest that responses to arachidonic acid are mediated in large part by the formation of TxA2 and provide evidence in support of the hypothesis that a discrete TxA2 receptor unrelated to PGF2 alpha or PGD2 receptors is present in undefined resistance vessel elements in the feline pulmonary vascular bed.

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

PubMed1992

Differential effects of PACAP and VIP on the pulmonary and hindquarters vascular beds of the cat.

Responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide derived from ovine hypothalamus with 68% sequence homology with vasoactive intestinal polypeptide (VIP), were investigated in the pulmonary and hindquarters vascular beds of the anesthetized cat under conditions of controlled blood flow. Injection of the peptide into the perfused lung lobe under elevated tone conditions produced dose-dependent decreases in lobar arterial pressure that were accompanied by biphasic changes in systemic arterial pressure characterized by an initial decrease followed by a secondary increase in pressure. When compared with other vasodilator agents in the pulmonary vascular bed, the relative order of potency was isoproterenol greater than PACAP greater than acetylcholine greater than calcitonin gene-related peptide greater than VIP. In the hindquarters vascular bed, intra-arterial injections of PACAP produced biphasic changes in hindquarters perfusion pressure characterized by initial decreases followed by secondary increases, which were accompanied by biphasic changes in systemic arterial pressure. In terms of relative vasodilator activity in the hindlimb, the order of relative potency was isoproterenol greater than acetylcholine greater than calcitonin gene-related peptide greater than VIP greater than PACAP. PACAP was the only agent that caused a secondary vasoconstrictor response in the hindlimb and produced biphasic changes in systemic arterial pressure. D-Phe2-VIP, a VIP receptor antagonist, blocked the hindquarters vasodilation in response to VIP but had no effect on responses to PACAP. The present investigation shows that PACAP produces pulmonary vasodilation, as well as dilation, and vasoconstriction in the systemic (hindlimb) vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Daltroban blocks thromboxane responses in the pulmonary vascular bed of the cat.

The influence of daltroban (BM13.505; SK&F 96148), a thromboxane (Tx) A2-receptor-blocking agent, on responses to the TxA2 mimics U-46619 and U-44069 was investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. Daltroban (5 mg/kg iv) had no significant effect on mean baseline vascular pressures but significantly decreased responses to the TxA2 mimics without altering responses to prostaglandin (PG) F2 alpha or PGD2 or the PGD2 metabolite 9 alpha, 11 beta-PGF2. Dose-response curves for U-46619 and U-44069 were shifted to the right in a parallel manner, and daltroban had no significant effect on responses to norepinephrine, serotonin, angiotensin II, BAY K 8644, endothelin-(ET) 1, ET-2, or platelet-activating factor (PAF). After administration of daltroban, responses to U-46619 returned to 50% of control in 90 min and responses to the PG and TxA2 precursor arachidonic acid were decreased significantly. These results suggest that daltroban selectively antagonizes TxA2-receptor-mediated responses in a competitive and reversible manner. These data provide support for the hypothesis that discrete TxA2 receptors unrelated to receptors stimulated by PGF2 alpha, PGD2, or 9 alpha, 11 beta-PGF2 are present in the pulmonary vascular bed of the cat. The present data suggest that pulmonary vasoconstrictor responses to PAF and ET peptides are not dependent on activation of TxA2 receptors in the cat.

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

PubMed1992

Inhibitory effects of DuP 753 and EXP3174 on responses to angiotensin II in pulmonary vascular bed of the cat.

The effects of the non-peptide antagonist DuP 753 and its metabolite EXP3174 on responses to angiotensin II were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure, injections of angiotensin II into the perfused lobar artery caused dose-related increases in lobar arterial pressure. Responses to angiotensin II were reproducible and were not changed by meclofenamate or prazosin, indicating that prostaglandin or norepinephrine release does not mediate or modulate pulmonary vascular responses to the peptide. DuP 753 (1-5 mg/kg iv) decreased responses to angiotensin II in a competitive manner, and the duration of the blockade was related to dose of the antagonist. DuP 753 had no significant effect on responses to U-46619, norepinephrine, serotonin, endothelin-1, vasopressin, or BAY K 8644. EXP3174 also decreased responses to angiotensin II without altering responses to agents that act by a variety of mechanisms. The inhibitory effect of EXP3174 (1 mg/kg iv) was not overcome by angiotensin II in the range of doses studied, and the shift to the right of the dose-response curve was nonparallel, suggesting that the blockade was noncompetitive. The blockade was long in duration, and, when the dose of EXP3174 was decreased to 0.1 mg/kg iv, the blockade was surmounted and the shift to the right of the dose-response relationship was parallel. DuP 753 and EXP3174 had little effect on mean baseline pressures in the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Pulmonary vasodilator response to vagal stimulation is blocked by N omega-nitro-L-arginine methyl ester in the cat.

The effect of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor production, on the vasodilator response to efferent vagal stimulation was 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 increased with U46619, efferent vagal stimulation decreased lobar arterial pressure in a stimulus-frequency-dependent manner. The decreases in lobar arterial pressure were enhanced by pretreatment with reserpine, were blocked by atropine, and were not altered by propranolol, indicating that the neurogenic vasodilator response was cholinergic in nature. The decreases in lobar arterial pressure in response to vagal stimulation and to exogenously administered acetylcholine were reduced after administration of L-NAME (100 mg/kg i.v.). Although L-NAME decreased pulmonary vasodilator responses to vagal stimulation and to acetylcholine, responses to adenosine, nicorandil, lemakalim, isoproterenol, prostaglandin E1, sodium nitroprusside, and 8-bromo-cGMP, agents that act by a variety of mechanisms, were not decreased. These results are consistent with the hypothesis that efferent vagal stimulation releases acetylcholine, which dilates the pulmonary vascular bed by stimulating the production of nitric oxide or a labile nitroso compound from L-arginine.

Animals↗

PubMed1991

Influence of lemakalim on the pulmonary vascular bed of the cat.

Pulmonary vascular responses to the K+ATP channel opener, lemakalim, were investigated in the intact-chest cat under constant flow conditions. When tone in the pulmonary vascular bed was elevated, intralobar injections of lemakalim caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. Lemakalim was approximately 3-fold more potent than cromakalim in dilating the pulmonary vascular bed, and pulmonary vasodilator responses to these K+ATP channel openers were blocked by the K+ATP channel blocking agent, glybenclamide. Glybenclamide had no significant effect on pulmonary vasodilator responses to acetylcholine or vasoactive intestinal peptide (VIP) but decreased responses to calcitonin gene-related peptide (CGRP). These data show that lemakalim has potent pulmonary vasodilator activity and suggest that responses are due to activation of a glybenclamide-sensitive K+ATP channel.

Animals↗

PubMed1991

Pulmonary vasodilator responses to RP 52891 are mediated by activation of a glibenclamide-sensitive K+ATP channel.

Pulmonary vasodilator responses to the K+ATP channel opener, RP 52891, were investigated in the intact-chest cat under constant flow conditions. When pulmonary vascular tone was increased with U46619, intralobar injections of RP 52891 caused dose-related decreases in lobar arterial and systemic arterial pressures without altering left atrial pressure. RP 52891 was more potent than pinacidil but less potent than cromakalim in dilating the pulmonary vascular bed. Pulmonary vasodilator responses to RP 52891, cromakalim and pinacidil, but not to acetylcholine, nitroprusside or isoproterenol, were blocked by glibenclamide. These data demonstrate that RP 52891 has potent pulmonary vasodilator activity in the cat and suggest that responses are due to opening of a glibenclamide-sensitive K+ATP channel.

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

PubMed1991

Pulmonary vascular and airway responses to endothelin-1 are mediated by different mechanisms in the cat.

The role of cyclooxygenase product formation and thromboxane A2 receptor activation in the response to endothelin-1 (ET-1) was investigated and compared in the airways and in the pulmonary vascular bed of the intact-chest cat. Intravenous injections of ET-1, 0.3 nmol/kg, increased lung resistance and decreased dynamic compliance. Bronchoconstrictor responses to ET-1 were decreased significantly by a cyclooxygenase inhibitor and by a thromboxane receptor blocking agent. In the pulmonary vascular bed of the cat under constant flow conditions, ET-1 increased lobar arterial pressure in a dose-related manner, and pulmonary vasconstrictor responses to the peptide were not altered by a cyclooxygenase inhibitor or thromboxane receptor blocking agent. The cyclooxygenase inhibitor blocked responses to the prostaglandin precursor, arachidonic acid; and the thromboxane receptor blocking agent reduced responses to the thromboxane mimic, U-46619. The present data suggest that bronchoconstrictor responses to ET-1 are dependent on the release of arachidonic acid, the formation of prostaglandins, and activation of thromboxane A2 receptors whereas pulmonary vasoconstrictor responses to the peptide are mediated by a different mechanism.

Animals↗

PubMed1991

Influence of SQ 30741 on thromboxane receptor-mediated responses in the feline pulmonary vascular bed.

The effects of SQ 30741, a thromboxane A2 (TxA2) receptor blocking agent, on responses to the TxA2 mimic, U-46619, were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 30741 in doses of 1-2 mg/kg iv markedly reduced vasoconstrictor responses to U-46619 without altering responses to prostaglandin (PG) F2 alpha or PGD2 and serotonin. SQ 30741 had no significant effect on mean vascular pressures in the cat, and the dose-response curve for U-46619 was shifted to the right in a parallel manner with a similar apparent maximal response. In addition to not altering responses to PGF2 alpha, PGD2 alpha, or serotonin, SQ 30741 (2 mg/kg iv) was without significant effect on pulmonary vasoconstrictor responses to the PGD2 metabolite 9 alpha, 11 beta-PGF2, norepinephrine, angiotensin II, BAY K 8644, endothelin 1, or endothelin 2. Although responses to vasoconstrictor agents, which act through a variety of mechanisms, were not altered, responses to the PG and TxA2 precursor, arachidonic acid, were reduced significantly. The duration of the TxA2 receptor blockade was approximately 30 and 75 min at the 1- and 2-mg/kg iv doses of the antagonist, respectively. The present data show that SQ 30741 selectively blocks TxA2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed. These data suggest that responses to arachidonic acid are due in large part to the formation of TxA2 and that discrete TxA2 receptors unrelated to receptors activated by PGD2 or PGF2 alpha are most likely located in resistance vessel elements in the feline pulmonary vascular bed.

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

PubMed1991

Analysis of responses to sarafotoxin 6a and sarafotoxin 6c in the pulmonary vascular bed of the cat.

Pulmonary vascular responses to sarafotoxins 6a and 6c (S6a and S6c) were investigated in the intact-chest cat under constant flow conditions. Injections of S6a and S6c into the perfused lobar artery caused dose-related increases in lobar arterial pressure, increased left atrial pressure, and produced biphasic changes in systemic arterial (aortic) pressure. When left atrial pressure was maintained constant, injections of S6a, S6c, and endothelin 1 (ET-1) caused dose-related increases in lobar arterial pressure. The increases in lobar arterial pressure in response to S6a and S6c were not altered by treatment with a cyclooxygenase inhibitor or a thromboxane receptor blocking agent. Increases in lobar arterial pressure in response to S6a and S6c were not altered when airflow to the left lower lung lobe was interrupted by bronchial occlusion, and pressor responses were not diminished when the left lower lobe was perfused with low-molecular-weight dextran. Under conditions of controlled blood flow and constant left atrial pressure, S6a, S6b, S6c, and ET-1 had similar pressor activity, whereas the thromboxane A2 mimic, U-46619, had far greater activity when compared on a nanomolar basis. The present studies demonstrate that S6a and S6c have significant vasoconstrictor activity in the feline pulmonary vascular bed. These data suggest that pulmonary vasoconstrictor responses to the endothelin peptides are not dependent on release of cyclooxygenase products and the activation of thromboxane A2 receptors, alterations in bronchomotor tone, or interaction with formed elements in blood.

Amino Acid Sequence↗

PubMed1991

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

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.

Acetylcholine↗

PubMed1991

Retroperitoneal necrotizing fasciitis.

We present a case of retroperitoneal necrotizing fasciitis treated by urgent abdomino-perineal resection of the rectum with permanent colostomy. We can find no prior case in the English literature treated in this manner. Retroperitoneal occurrence of this disease is unusual. The process originated from perianal sepsis following chemotherapy for head and neck cancer.

Adult↗

PubMed1989

The significance of alkalosis and hypochloremia in hypertrophic pyloric stenosis.

Hypochloremic alkalosis is the "classical" electrolyte abnormality seen in hypertrophic pyloric stenosis (HPS), yet it occurs in only about half the patients. To define the clinical differences between infants who were alkalotic or hypochloremic and those who were not, we reviewed the records of 216 patients treated for HPS over a recent 5-year period at our institution. The 202 patients who had a full set of serum electrolytes drawn on admission were divided into nonalkalotic and alkalotic bicarbonate groups A (less than or equal to 25 mEq/L, n = 105) and B (greater than 25 mEq/L, n = 97) and also nonhypochloremic and hypochloremic chloride groups A (greater than or equal to 99 mEq/L, n = 117) and B (less than 99 mEq/L, n = 85). The alkalotic group B had a significantly higher proportion of black patients (17.5% v 8%), longer mean duration of illness (17.8 v 9.4 days), higher incidence of palpable pyloric mass (97% v 82%), greater degree of dehydration, lower mean serum sodium (136.3 v 137.7 mEq/L), lower mean serum potassium (4.50 v 5.15 mEq/L), and lower mean serum chloride (92.4 v 102.3 mEq/L) than did the nonalkalotic group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkalosis↗