Biomedical subjects

J A Santiago

Publications and source records attributed to J A Santiago.

At least 19 recordsLinked to original sources

PubMed2005

Sequential mitoxantrone/prednisone followed by docetaxel/estramustine in patients with hormone refractory metastatic prostate cancer: results of a phase II study.

BACKGROUND: Mitoxantrone/prednisone ameliorates symptoms in hormone refractory prostate cancer (HRPC) but has no effect on survival. Docetaxel (Taxotere)/estramustine improves response but with significant toxicity. We reasoned that a sequential administration of the two regimens could be a viable alternative for delivering full doses of chemotherapy, avoiding overlapping toxicity and preserving dose intensity. PATIENTS AND METHODS: Thirty HRPC patients were treated with mitoxantrone 10 mg/m(2), day 1, every 3 weeks, plus prednisone 5 mg twice daily, for three cycles, followed by estramustine phosphate, 280 mg three times daily, days 1 to 5, plus docetaxel 75 mg/m(2), day 2, every 3 weeks for a maximum of 10 cycles. RESULTS: All patients were assessable for response and toxicity. After mitoxantrone/prednisone treatment, the prostate-specific antigen (PSA) response rate was 23%, which increased to 63% after completion of sequential mitoxantrone/prednisone and docetaxel/estramustine treatment (12 partial and 7 complete responses). With a median follow-up of 18 months, median survival for all patients was 18 months, and median progression-free survival was 10 months. The mitoxantrone/prednisone regimen was well tolerated, and the only grade 3-4 toxicity was grade 3 neutropenia in four (13%) patients. Twenty-nine patients received a total of 173 cycles of docetaxel/estramustine (median, 6 cycles/patient). Six (20%) patients had grade 3-4 neutropenia and two (6%) patients had febrile neutropenia episodes. The most frequent non-hematological toxic effects were asthenia, nausea and vomiting, edemas and onycholysis. Two (6%) patients had deep venous thrombosis. CONCLUSIONS: Mitoxantrone/prednisone followed by docetaxel/estramustine is a well-tolerated and active regimen in HRPC. Sequential therapy is feasible and can be used to integrate novel, more active regimens.

Aged↗

PubMed2004

Peroxynitrite does not impair pulmonary and systemic vascular responses.

The effects of peroxynitrite (ONOO-) on vascular responses were investigated in the systemic and hindquarters vascular bed and in the isolated perfused rat lung. Intravenous injections of ONOO- decreased systemic arterial pressure, and injections of ONOO- into the hindquarters decreased perfusion pressure in a dose-related manner. Injections of ONOO- into the lung perfusion circuit increased pulmonary arterial perfusion pressure. Responses to ONOO- were rapid in onset, short in duration, and repeatable without exhibiting tachyphylaxis. Repeated injections of ONOO- did not alter systemic, hindquarters, or pulmonary responses to endothelium-dependent vasodilators or other vasoactive agonists and did not alter the hypoxic pulmonary vasoconstrictor response. Injections of sodium nitrate or nitrite or decomposed ONOO- had little effect on vascular pressures. Pulmonary and hindquarters responses to ONOO- were not altered by a cyclooxygenase inhibitor in a dose that attenuated responses to arachidonic acid. These results demonstrate that ONOO- has significant pulmonary vasoconstrictor, systemic vasodepressor, and vasodilator activity; that short-term repeated exposure does impair vascular responsiveness; and that responses to ONOO- are not dependent on cyclooxygenase product release.

Anesthesia↗

PubMed2002

Lipid membranes with an edge.

Consider an open lipid membrane with a free exposed edge. The energy describing this membrane is quadratic in the extrinsic curvature; that describing the edge is proportional to its length. We determine the boundary conditions satisfied by the equilibria of the membrane on this edge. The derivation is free of any assumptions on the symmetry of the membrane geometry. With respect to the axially symmetric case, there is an additional boundary condition that is identically satisfied in that limit. By considering the balance of the forces operating at the edge, a physical interpretation for the boundary conditions is provided. The effect of the addition of a Gaussian rigidity term for the membrane is also considered.

Journal Article↗

PubMed1997

Differential effects of glibenclamide on responses to thromboxane A2 mimic, U46619, in the pulmonary and hindquarters vascular beds of the cat.

The inhibitory effects of the oral sulfonylurea, glibenclamide, on vasoconstrictor responses to the thromboxane A2 mimic, U46619, were investigated in the pulmonary and hindquarters vascular beds of the cat under constant flow conditions. When lobar arterial tone was at resting conditions (14 +/- 2 mm Hg), intralobar injections of U46619, prostaglandin F2alpha, prostaglandin D2, angiotensin II, norepinephrine, and BAY K 8644 caused dose-related increases in lobar arterial pressure without altering left atrial pressure. Following an intralobar infusion of glibenclamide (5 mg/kg), vasoconstrictor responses to U46619, prostaglandin F2alpha and prostaglandin D2 were significantly reduced, whereas vasoconstrictor responses to norepinephrine and angiotensin II were not altered and responses to BAY K 8644 were significantly enhanced. When tone in the pulmonary vascular bed was raised to a high steady level (36 +/- 3 mm Hg), glibenclamide in a dose of 5 mg/kg i.a. markedly attenuated responses to injections of U46619 and reduced the vasodilator responses to the K+-ATP channel opener, levcromakalim, whereas responses to acetylcholine and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, were not changed. In the hindquarters vascular bed of the cat, administration of glibenclamide in a dose of 5 mg/kg i.a. had no significant effect on vasoconstrictor responses to U46619, norepinephrine or angiotensin II. Hindquarters vasodilator responses to levcromakalim, but not to nitric oxide, were decreased significantly following administration of glibenclamide. These data suggest that glibenclamide, in addition to inhibiting K+-ATP channels, has thromboxane A2 receptor blocking activity in the pulmonary vascular bed of the cat. These data also suggest that vasoconstrictor responses to U46619 may be mediated by different thromboxane A2 receptors with different binding affinities in the pulmonary and in the hindquarters vascular beds of the cat.

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

PubMed1997

Comparison of responses to T-kinin and bradykinin in the mesenteric vascular bed of the cat.

Responses to T-kinin and bradykinin were compared in the mesenteric vascular bed of the cat. Under constant-flow conditions, injection of T-kinin and bradykinin into the perfusion circuit induced similar dose-related decreases in perfusion pressure. Responses to T-kinin and bradykinin were inhibited by the kinin B2 receptor antagonist Hoe-140, but were not altered by the B1 receptor antagonist des-Arg9-[Leu8]-BK, the histamine H1 antagonist pyrilamine, the histamine H2 receptor antagonist cimetidine, or the H3 receptor antagonist thioperamide. Vasodilator responses to T-kinin and bradykinin were attenuated by the nitric oxide synthase inhibitor, N omega Nitro-L-arginine methyl ester (L-NAME), but were not altered by the cyclooxygenase inhibitor, sodium meclofenamate, or the K+ ATP channel antagonist, U37883A. These data suggest that vasodilator responses to T-kinin and bradykinin are mediated by kinin B2 receptor stimulated release of nitric oxide from the endothelium, but that the activation of kinin B1 receptors, the release of vasodilator prostaglandins, or the opening of K+ ATP channels are not involved in the response to T-kinin in the mesenteric vascular bed of the cat.

Adamantane↗

PubMed1997

T-kinin has endothelium-dependent vasodilator activity in the cat.

Responses to T-kinin, a peptide formed from the acute-phase substrate T-kininogen, were investigated in the hindlimb vascular bed of the cat. Under constant-flow conditions, injections of T-kinin into the perfusion circuit in doses of 0.03-1 nmol induced rapid dose-related decreases in perfusion pressure. Responses to T-kinin were similar in time course and magnitude to responses to bradykinin and kallidin and were inhibited by the kinin B2-receptor antagonist, Hoe-140. Responses to T-kinin were attenuated by an inhibitor of nitric oxide synthase and by tetraethylammonium chloride and were enhanced in duration by the guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor zaprinast. Responses to T-kinin were not altered by inhibitors of K+(ATP) channels, by the cyclooxygenase pathway, or by muscarinic or beta-adrenergic-receptor antagonists. These data suggest that vasodilator responses to T-kinin are mediated by kinin B2-receptor-stimulated release of nitric oxide from the endothelium and increased smooth muscle cGMP levels. These results indicate that activation of K+(ATP) channels and muscarinic or beta-adrenergic receptors and the release of vasodilator prostaglandins are not involved in mediating the response to T-kinin in the hindlimb circulation of the cat.

Acetylcholine↗

PubMed1997

Adrenomedullin-(22-52) antagonizes vasodilator responses to CGRP but not adrenomedullin in the cat.

The effects of adrenomedullin (ADM)-(22-52), a putative ADM receptor antagonist, on vasodilator responses to ADM and the structurally related peptide, calcitonin gene-related peptide (CGRP), were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. ADM-(22-52) had no significant effect on hindlimb perfusion pressure when injected in doses up to 120 nmol; after administration of ADM-(22-52), vasodilator responses to ADM were unchanged, whereas vasodilator responses to CGRP were inhibited. The inhibitory effects of ADM-(22-52) on responses to CGRP were selective and reversible and were similar to the inhibitory effects of the CGRP antagonist CGRP-(8-37). Hindlimb vasodilator responses to CGRP and to ADM were increased in duration by the adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor rolipram but were not altered by inhibitors of guanosine 3',5'-cyclic monophosphate phosphodiesterase, nitric oxide synthetase, K(+)-ATP channels, the cyclooxygenase pathway, or the adrenergic nervous system. These results demonstrate that ADM-(22-52) is a selective CGRP receptor antagonist in the hindlimb vascular bed of the cat. The present data suggest that vasodilator responses to CGRP and ADM are mediated by different receptors but that these peptides dilate the hindlimb vascular bed of the cat by a similar cAMP-dependent mechanism.

Adrenomedullin↗

PubMed1997

Analysis of responses to human synthetic adrenomedullin and calcitonin gene-related peptides in the hindlimb vascular bed of the cat.

Vasodilator responses to human adrenomedullin (hADM), a newly discovered hypotensive peptide, human calcitonin gene-related peptide-alpha (hCGRP-alpha) and hCGRP-beta, which share structural homology with hADM, were compared in the hindlimb vascular bed of the cat under constant flow conditions. Injections of hADM (0.003-1 nmol), hCGRP-alpha, and hCGRP-beta (0.003-0.3 nmol) into the perfusion circuit caused dose-related decreases in hindlimb perfusion pressure. Vasodilator responses to hCGRP-alpha and hCGRP-beta were similar in potency and duration, and the doses of hCGRP-alpha and hCGRP-beta required to reduce hindlimb perfusion pressure 40 mm Hg (ED40 mm Hg) were significantly lower than the ED40 mm Hg for hADM. The duration of the hindlimb vasodilator responses to hCGRP-alpha and hCGRP-beta were significantly longer than the duration of the response to hADM. Amylin, a peptide that shares structural homology with ADM and with CGRP, had no significant effect on hindlimb perfusion pressure when injected in doses up to 1 nmol. Decreases in hindlimb perfusion pressure in response to hADM, hCGRP-alpha, and hCGRP-beta were not altered by L-N5-(1-iminoethyl)-ornithine (L-NIO) in a dose of the nitric oxide synthase inhibitor that decreased the vasodilator response to acetylcholine or by the cyclooxygenase inhibitor, meclofenamate, in a dose that decreased the vasodilator response to archidonic acid. The present data demonstrate that hADM, hCGRP-alpha, and hCGRP-beta have potent, but relatively short-lasting, vasodilator activity, and that vasodilator responses are not dependent on the release of nitric oxide or vasodilator prostaglandins in the hindlimb vascular bed of the cat.

Acetylcholine↗

PubMed1996

Analysis of cardiovascular responses to PACAP-27, PACAP-38, and vasoactive intestinal polypeptide.

Responses to pituitary adenylate cyclase polypeptide (PACAP)-27, PACAP-38, and vasoactive intestinal peptide (VIP) were compared in the peripheral and pulmonary vascular beds of the cat and in the isolated perfused neonatal pig heart. Intravenous injections of PACAP-27 and PACAP-38 produced biphasic changes in systemic arterial pressure whereas iv injections of VIP caused only decreases in arterial pressure. When blood flow to the hind limb and mesenteric vascular beds was maintained constant, PACAP-27 and PACAP-38 caused dose-related biphasic changes in perfusion pressure, whereas VIP only decreased perfusion pressure. PACAP-27 was approximately threefold more potent than PACAP-38, and the pressor component of the biphasic response was blocked by alpha-adrenergic antagonists and adrenalectomy. PACAP-27, PACAP-38, and VIP produced decreases in pulmonary vascular resistance, and all three peptides had significant vasodilator activity in the isolated perfused neonatal pig heart. Although all three peptides decreased coronary vascular resistance, only PACAP-27 and PACAP-38 increased left ventricular contractility, with PACAP-27 approaching isoproterenol in potency. The results of these experiments show that PACAP-27, PACAP-38, and VIP have significant effects on vasomotor tone that depend on the vascular bed studied and the contribution of adrenal catecholamines.

Amino Acid Sequence↗

PubMed1995

Comparison of responses to adrenomedullin and adrenomedullin analogs in the mesenteric vascular bed of the cat.

Responses to adrenomedullin, a newly discovered hypotensive peptide isolated from human pheochromocytoma cells, and the carboxy terminal 15-52 (adrenomedullin-(15-52)) and 22-52 (adrenomedullin-(22-52)) amino acid fragments of adrenomedullin were investigated in the mesenteric vascular bed of the cat. Under constant flow conditions, injections of adrenomedullin, adrenomedullin-(15-52), and calcitonin gene-related peptide (CGRP) in doses of 0.003-1 nmol into the perfused superior mesenteric artery caused significant dose-related decreases in mesenteric arterial perfusion pressure. Mesenteric vasodilator responses to adrenomedullin and adrenomedullin-(15-52) were similar in magnitude and duration, while vasodilator responses to CGRP were greater in magnitude and longer in duration than those produced by adrenomedullin or adrenomedullin-(15-52) when these agents were injected in doses of 0.1-1 nmol. Adrenomedullin-(22-52) caused no significant change in mesenteric arterial perfusion pressure when injected in doses up to 10 nmol. These results suggest that amino acids 15-52 and the six-membered ring structure of adrenomedullin are important for the expression of vasodilator activity in the mesenteric vascular bed of the cat.

Adrenomedullin↗

PubMed1995

Analysis of responses to angiotensin peptides in the hindquarters vascular bed of the cat.

Responses to angiotensin I, II, III, and IV, des-Asp1-angiotensin I, and (p-amino-Phe6)-angiotensin II were compared in the hindquarters vascular bed of the cat. The peptides produced dose-related increases in perfusion pressure, and dose-response curves to all six peptides were parallel. Des-Asp1-angiotensin I, angiotensin I, II, and III produced similar increases in perfusion pressure and were approximately 300-fold more potent than (p-amino-Phe6)-angiotensin II, 100-fold more potent than angiotensin IV, 30-fold more potent than norepinephrine, and 10-fold more potent than U-46619. The time courses of the response to des-Asp1-angiotensin I, angiotensin I, II, and III were similar, and responses were not altered by a time-delay coil. DuP-532, an AT1 receptor antagonist, reduced responses to the six angiotensin peptides. PD-123,319 did not alter responses to the angiotensin peptides. The angiotensin-converting enzyme inhibitor captopril reduced responses to angiotensin I and des-Asp1-angiotensin I. These results show that des-Asp1-angiotensin I as well as angiotensin I, II, III, and IV have similar efficacy and that responses to the peptides and (p-amino-Phe6)-angiotensin II are mediated by AT1 receptors. These results suggest that AT2 receptors have little role in modulating responses and that angiotensin IV has a lower affinity for the AT1 receptor than does angiotensin II or III. The results also indicate that complete rapid local conversion of the substrates into active peptides occurs near the site of action within the hindquarters vascular bed.

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

PubMed1995

Role of K+ATP channels and EDRF in reactive hyperemia in the hindquarters vascular bed of cats.

The mechanism underlying reactive hyperemia was investigated in the feline hindquarters vascular bed under natural- and constant-flow conditions. A 30-s occlusion of the distal aorta produced a marked hyperemic increase in distal aortic blood flow that was attenuated by the ATP-sensitive K+ (K+ATP) channel blocking agent, glibenclamide. When blood flow to the hindquarters vascular bed was held constant with a pump, interruption of blood flow for 5- to 90-s periods produced reactive vasodilator responses that increased in magnitude and duration as the period of ischemia increased. The magnitude and duration of the reactive vasodilator responses were reduced by K+ATP channel antagonists and an inhibitor of nitric oxide synthase, whereas indomethacin had no significant effect. In the pulmonary vascular bed, under constant-flow, elevated tone conditions, a 30-s period of ischemia produced a small reactive vasodilator response and a larger secondary vasoconstrictor response. The present data suggest that reactive hyperemia in the hindquarters vascular bed is mediated by the opening of K+ATP channels and nitric oxide release and that the reactive hyperemic response is not pronounced in the pulmonary circulation.

Adamantane↗

PubMed1995

Analysis of responses to kallidin, DABK, and DAK in feline hindlimb vascular bed.

Responses to kallidin, des-Arg9-bradykinin (DABK), and des-Arg10-kallidin (DAK) were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. Injections of kallidin, DABK, and DAK into the hindlimb perfusion circuit produced dose-dependent vasodilator responses in the hindlimb vascular bed. Vasodilator responses to kallidin and bradykinin (BK) were similar in magnitude and time course, and both peptides were approximately 100-fold more potent than DABK or DAK. Responses to kallidin were decreased by the kinin B2 antagonist, HOE 140, whereas responses to DABK and DAK were reduced by des-Arg9[Leu8]BK, a kinin B1-receptor antagonist. N omega-nitro-L-arginine methyl ester (L-NAME) reduced vasodilator responses to kallidin, DABK, and DAK, whereas meclofenamate, atropine, and U-37883A, a vascular selective ATP-sensitive K+ (K+ATP) channel-blocking agent, did not alter responses to the three peptides. These data suggest that both kinin B1 and B2 receptors are normally present in the hindlimb vascular bed. These data also suggest that kinin B1 and B2 receptor-mediated vasodilator responses are mediated by the release of nitric oxide and that the activation of K+ATP channels or muscarinic receptors, or the release of vasodilator prostaglandins play little if any role in mediating responses to kallidin, DABK, or DAK in the hindlimb vascular bed of the cat.

Adamantane↗

PubMed1994

Comparative effects of N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance P.

N omega-Nitro-L-arginine methyl ester has been reported to have muscarinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, undertaken to compare the inhibitory effects of N omega-nitro-L-arginine methyl ester with those of N omega-nitro-L-arginine on baseline tone and on vasodilator responses to acetylcholine, bradykinin, and substance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine in doses of 100 mg/kg i.v. increased baseline tone in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator agents following administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine did not differ significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine but did not alter responses to bradykinin or substance P. The similarity in the inhibitory effects of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine on responses to acetylcholine, bradykinin, and substance P suggest that the L-arginine analog, N omega-nitro-L-arginine, as well as the methyl ester of N omega-nitro-L-arginine, are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascular bed of the cat.

Acetylcholine↗

PubMed1994

Synthetic human adrenomedullin and adrenomedullin 15-52 have potent short-lived vasodilator activity in the hindlimb vascular bed of the cat.

Responses to synthetic human adrenomedullin, a novel hypotensive peptide isolated from human pheochromocytoma cells, and the carboxy terminal 15-52 amino acid fragment of adrenomedullin (ADM15-52) were investigated in the hindlimb vascular bed of the cat under constant flow conditions. Intraarterial injections of the peptides in doses of 0.01-0.3 nmol caused dose-related decreases in hindlimb perfusion pressure. When compared on a nmol basis, adrenomedullin and ADM15-52 were similar to bradykinin in vasodilator potency and were approximately 10 fold less potent than acetylcholine. The half-life of the vasodilator response to adrenomedullin and ADM15-52 ranged from 55 to 80 sec and was greater than the half-life of vasodilator responses to bradykinin in doses of 0.01-0.3 nmol and acetylcholine in doses of 0.01-0.3 nmol. The present data demonstrate that synthetic human adrenomedullin and ADM15-52 have potent but relatively short-lasting vasodilator activity in the hindlimb vascular bed of the cat. These data suggest that amino acid residues 15-52 of adrenomedullin are important for the expression of vasodilator activity in the hindlimb vascular bed of the cat.

Adrenomedullin↗

PubMed1994

Analysis of responses to bradykinin: effects of Hoe-140 in the hindquarters vascular bed of the cat.

The mechanisms and receptor subtype mediating vasodilator responses to bradykinin were investigated in the hindquarters vascular bed of the cat under constant flow conditions. Intraarterial injections of bradykinin in doses of 10-1,000 ng into the hindquarters vascular bed caused dose-related decreases in perfusion pressure that were inhibited by Hoe-140, a bradykinin B2-receptor antagonist. Injections of des-Arg9-bradykinin (in doses 10-fold higher than for bradykinin) caused smaller dose-related decreases in hindquarters perfusion pressure that were not blocked by Hoe-140. Administration of atropine, glibenclamide, or cyclooxygenase inhibitors did not alter vasodilator responses to bradykinin, suggesting that activation of muscarinic receptors, ATP-sensitive K+ channels, or prostaglandin release is not involved in the response to the peptide. Administration of N omega-nitro-L-arginine and its methyl ester reduced vasodilator responses to bradykinin, acetylcholine, and substance P, whereas responses to endothelium-independent vasodilator agents were not attenuated. Decreases in systemic arterial pressure and in hindquarters perfusion pressure in response to bradykinin were enhanced by the angiotensin-converting enzyme inhibitors captopril and enalaprilat. These results suggest that hindquarters vasodilator responses to bradykinin are mediated by activation of kinin B2 receptors and in part by the release of nitric oxide. These data also suggest the presence of bradykinin B1 receptors, mediating vasodilation in the hindquarters vascular bed. These results indicate that bradykinin is rapidly inactivated by angiotensin-converting enzyme in the lung and in the hindquarters vascular bed of the cat.

Animals↗

PubMed1993

Analysis of responses to pituitary adenylate cyclase activating polypeptide-38 in the feline hindquarters vascular bed.

Responses to pituitary adenylate cyclase activating polypeptide (PACAP)-38 were investigated and compared with responses to PACAP-27 and vasoactive intestinal polypeptide (VIP) in the hindquarters vascular bed of the cat under constant flow conditions. Injections of PACAP-38 into the hindquarters perfusion circuit caused dose-related, biphasic changes characterized by initial decreases followed by increases in both hindquarters perfusion and systemic arterial pressure. In relative terms, PACAP-38 was less potent then PACAP-27 and VIP in dilating the hindquarters vascular bed, with the order of related potency being VIP > PACAP-27 > PACAP-38 when the doses required to decrease hindquarters perfusion pressure by 25 mm Hg were compared. When comparing the relative vasoconstrictor activity of PACAP-38 to that of PACAP-27 and norepinephrine, PACAP-38 was approximately 3-fold less potent than PACAP-27 and 10-fold less potent than norepinephrine. The vasoconstrictor component of the response to PACAP-38 and, as shown previously, for PACAP-27 was blocked by phentolamine in a dose that significantly reduced pressor responses to norepinephrine in the hindquarters vascular bed. The present data show that PACAP-38 has significant vasodilator and vasoconstrictor activity in the hindquarters vascular bed of the cat, and that the 27 amino acid form of the peptide has greater depressor and pressor activity than PACAP-38.

Animals↗

PubMed1993

Inhibitory effects of Hoe 140 on vasodilator responses to bradykinin in the mesenteric vascular bed of the cat.

The effect of Hoe 140, a bradykinin B2 receptor antagonist, on vasodilator responses to bradykinin was investigated in the mesenteric vascular bed of the cat under constant flow conditions. Injections of bradykinin into the mesenteric vascular bed induced dose-related decreases in perfusion pressure which were reduced significantly following administration of Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) (100 micrograms/kg i.v.). The inhibitory effects of Hoe 140 were longer than 3 h in duration and vasodilator response to acetylcholine and S-nitroso-N-acetylpenicillamine and vasoconstrictor responses to norepinephrine, angiotensin II, and the thromboxane mimic, U46619 (9,11-dideoxy-11 alpha,9 alpha-epoxymethano-prostaglandin F2 alpha) were unchanged by the B2 receptor antagonist. Hoe 140 had little effect on baseline systemic arterial and mesenteric arterial perfusion pressures. These results suggest that Hoe 140 is a potent, highly selective, long-acting bradykinin B2 receptor antagonist with little agonistic activity in the mesenteric vascular bed of the cat.

Acetylcholine↗