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R Couture

Publications and source records attributed to R Couture.

At least 19 recordsLinked to original sources
PubMed1995

Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat.

1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiotensin AT1 (losartan and its active metabolite EXP 3174), angiotensin AT2 (PD 123,319) or tachykinin NK3 (R 486) receptors. 2. I.c.v. administration of 25 pmol AII evoked an increase in mean arterial blood pressure (MAP) and water intake behaviour, accompanied by a transient bradycardia, whereas 25 pmol [MePhe7]NKB caused a transient increase in MAP and heart rate (HR) concurrently with marked wet dog shake behaviour. At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours. 3. Losartan (650 pmol, i.c.v.) reduced significantly the cardiovascular and behavioural responses to AII or [MePhe7]NKB, but not to SP or NKA. While 65 pmol losartan was inactive, 260 pmol inhibited selectively the central effects of AII. Whereas EXP 3174 (6.5 nmol) blocked both AII and [MePhe7]NKB-mediated responses, the dose of 650 pmol blocked only the responses to AII. 4. The central responses to AII and [MePhe7]NKB were not affected by PD 123,319 (650 pmol). On the other hand, the [MePhe7]NKB-induced central effects were significantly reduced by R 486 (650 pmol). The NK3-selective antagonist had no effect against AII. 5. This study provides functional evidence, to support earlier binding data, that losartan (and to some extent its active metabolite EXP 3174) interact with the tachykinin NK3 receptor in rat brain. However,the cardiovascular and behavioural responses induced by central tachykinin agonists (SP, NKA and[MePhe7]NKB) and All are mediated by unrelated mechanisms.

Angiotensin II↗
PubMed1995

Modulatory effect of bradykinin on the release of noradrenaline from rat isolated atria.

1. We investigated the modulation by bradykinin (BK) of electrically induced noradrenaline release in rat isolated atria preincubated with [3H]-noradrenaline. 2. BK (1-100 nM) enhanced significantly the stimulation-induced outflow of radioactivity in a concentration-dependent manner with a calculated EC50 of 0.58 nM. 3. Des-Arg9-BK (0.1-100 nM), a selective B1 receptor agonist, did not modify the stimulation-induced outflow of radioactivity. Hoe 140 (10 nM), a selective B2 receptor antagonist, but not [Leu8]-des-Arg9-BK (100 nM), a selective B1 receptor antagonist, blocked the facilitatory effect of BK. 4. The effect of BK was not affected by diclofenac (1 microM), a cyclo-oxygenase inhibitor. Bisindolylmaleimide (1 microM), a protein kinase C inhibitor, significantly reduced the facilitatory effect of BK (10 nM), angiotensin II (0.3 microM) and phorbol dibutyrate (0.1 and 1 microM) but not of fenoterol (1 microM). 5. The results suggest that BK enhances noradrenaline release via a prejunctional B2 kinin receptor in the rat atrium. The effect appears to involve protein kinase C as a second messenger.

Adrenergic beta-Antagonists↗
PubMed1994

Cardiovascular effects of intrathecally administered endothelins and big endothelin-1 in conscious rats: receptor characterization and mechanism of action.

In conscious rats, the intrathecal (i.t.) injection of endothelin-1 (ET-1; 65-650 pmol) and endothelin-3 (ET-3; 162-650 pmol) produced dose-dependent increases of mean arterial blood pressure (MAP) accompanied by either a tachycardia or a bradycardia. A number of animals died by a sudden respiratory arrest. ET-3 was less toxic and less potent than ET-1 on MAP and heart rate (HR) while BQ-3020, a selective ETB agonist, had no toxic effect and exhibited only a weak pressor effect on blood pressure. The prior i.t. injection of 65 nmol BQ-123, a selective ETA receptor antagonist, blocked both the cardiovascular and toxic effects of ET-1 but failed to modify the cardiovascular effect evoked by i.t. substance P (6.5 nmol) or to cause intrinsic cardiovascular and toxic effects. While the pressor response to ET-1 was significantly inhibited after i.v. injection of phentolamine, the bradycardia was blocked by pentolinium. The cardiovascular response to ET-1 was, however, unaffected in rats either sympathectomized with 6-hydroxydopamine or pretreated with capsaicin. Furthermore, big ET-1 (100 pmol) caused toxic effects and delayed cardiovascular changes which were prevented by the prior i.t. administration of either BQ-123 (65 nmol) or 100 nmol phosphoramidon, an endothelin-converting enzyme (ECE) inhibitor. These results suggest: (1) that the cardiovascular and toxic effects of i.t. endothelins are mediated by ETA receptors in the rat spinal cord; (2) that the pressor response and bradycardia are likely due to the activation of the sympatho-adrenal nervous system and to a vagal reflex mechanism, respectively; and (3) that a phosphoramidon-sensitive ECE converts big ET-1 to ET-1 in the rat spinal cord.

Amino Acid Sequence↗
PubMed1994

Regional changes in the extravasation of albumin in the canine kidney: comparison of bradykinin and water diuresis.

This report describes the adaptation of the albumin bound Evans blue dye (EB) extraction technique and its use in identifying regional changes in albumin extravasation rates. We present data to justify our technical approach and highlight the use of this method by describing differences resulting from two different models of induced diuresis and natriuresis. Results observed under control conditions (Group 1) are compared to those obtained following the infusion of bradykinin (BK) into the left kidney (Group 2) or hypotonic saline-induced water diuresis (Group 3). EB and water content of tissue samples of cortex (CTX), outer medulla (OM), inner medulla (IM), and papilla (PAP) regions are reported. Under control conditions a significant heterogeneous distribution of EB and water content (wet/dry tissue weight) between zones was observed. Left kidney EB values for the CTX, OM, IM, and PAP in Group 1 were 125 +/- 11, 398 +/- 56, 763 +/- 51, and 741 +/- 52 micrograms EB/g dry tissue and respective wet/dry tissue ratios were 4.48 +/- 0.05, 5.10 +/- 0.19, 7.13 +/- 0.37, and 6.35 +/- 0.32. In Group 2, BK caused a selective increase in cortex EB content to 201 +/- 7 (P < 0.01) micrograms EB/g dry tissue, without altering water content values. Results of EB extraction in Group 3 revealed no change in the CTX but significant increases in the OM, IM, and PAP regions: 576 +/- 40 (P < 0.01), 910 +/- 60 (P < 0.01), and 850 +/- 69 (P < 0.05) micrograms EB/g dry tissue, respectively. Likewise, tissue water content values were unchanged in the CTX but significantly greater in the OM, IM, and PAP: 6.02 +/- 0.22, 8.90 +/- 0.25, and 8.40 +/- 0.17, respectively (P < 0.01, all three values). This technique clearly shows the regional heterogeneity of the renal microvascular network and allows the localization of intrarenal changes in albumin extravasation. This method provides evidence that BK increases albumin extravasation in the cortex only and that changes in the renal medulla are obtained in hypotonic saline-induced water diuresis.

Albumins↗
PubMed1994

Development of digoxigenin-labeled peptide: application to chemiluminoenzyme immunoassay of bradykinin in inflamed tissues.

A new ultrasensitive chemiluminoenzyme immunoassay (CLEIA) using digoxigenin-labeled bradykinin (BK) as a tracer is proposed to quantify kinins in tissue samples. Rabbit polyclonal IgGs anti-BK directed against the C-terminal end were used for the immunoconcentration step along with dioxetane derivative for the revelation step. The sensitivity of the assay for BK was 0.1 fmol/ml with ED50 of 0.78 pmol/ml. This method was applied on extracts of normal and carrageenan-inflamed tissues. The edema produced by the injection of carrageenan in rat hindpaws was associated with a sevenfold increase of immunoreactive kinins in the inflamed paw extract (from 0.021 +/- 0.007 to 0.141 +/- 0.021 pmol/g tissue; p < 0.01), the immunoreactivity corresponded to BK, kallidin, and T-kinin after HPLC separation. When a mixture of inhibitors of kininase I (mergepta) and kininase II (captopril) was coinjected with carrageenan, the carrageenan-induced edema was unaffected but the kinin tissue content was significantly enhanced (0.207 +/- 0.003 pmol/g tissue; p < 0.01). However, the kinin tissue content and the edema response were unaltered by inhibitors given separately. Hence, this highly sensitive assay provides a biochemical evidence that kinins may act as proinflammatory mediators, and highlights a compensatory increase of kininase I and II activities in inflamed tissues.

3-Mercaptopropionic Acid↗
PubMed1994

Cardiovascular and behavioural effects of centrally administered tachykinins in the rat: characterization of receptors with selective antagonists.

1. The effects of intracerebroventricular (i.c.v.) injection of selective and potent NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 486, [Trp7, beta-Ala8]NKA(4-10)) receptor antagonists were assessed on the cardiovascular and behavioural responses elicited by the i.c.v. injection of substance P (SP), neurokinin A (NKA) or [MePhe7]neurokinin B ([MePhe7]NKB) in the conscious freely moving rat. 2. SP, NKA and [MePhe7]NKB (5-650 pmol) evoked dose-dependent increases in mean arterial blood pressure (MAP) and heart rate (HR) with the rank order of potency SP > NKA > [MePhe7]NKB. The cardiovascular responses were accompanied by excessive face washing, grooming and wet dog shakes. 3. The cardiovascular effects and face washing behaviour induced by SP (25 pmol) were significantly reduced by the pre-injection (i.c.v., 5 min earlier) of RP 67580 (6.5 nmol). However, this antagonist failed to affect the central effects of 25 pmol NKA or [MePhe7]NKB. 4. The cardiovascular and behavioural responses (except for wet dog shakes) elicited by NKA (25 pmol) were significantly reduced by 6.5 nmol SR 48968. However, the latter antagonist had no effect on the SP or [MePhe7]NKB-mediated responses. 5. Both cardiovascular and behavioural effects produced by either SP or NKA (25 pmol) were completely abolished when rats were pretreated with a combination of RP 67580 (6.5 nmol) and SR 48968 (6.5 nmol), yet this combination of antagonists failed to modify the central effects of [MePhe7]NKB. 6. R 486 (6.5 nmol) inhibited the cardiovascular effects as well as wet dog shakes produced by [MePhe7]NKB, but it was inactive against the responses induced by either SP or NKA. 7. None of the tachykinin receptor antagonists or agonists caused motor impairment or respiratory distress. All antagonists blocked in a reversible manner and were devoid of intrinsic activity except R486 (6.5 nmol) which produced a transient increase of MAP and HR.8. These results suggest that the central effects of SP, NKA and [MePhe7]NKB are primarily mediated by central NK1, NK2 and NK3 receptors, respectively. However, a minor activation of NK2 receptors bySP and NK1 receptors by NKA was seen during blockade of both receptors. This study therefore supports the existence of functional NK1, NK2 and NK3 receptors in the adult rat brain.

Animals↗
PubMed1994

Cardiovascular and behavioural effects of centrally administered neuropeptide K in the rat: receptor characterization.

1. The cardiovascular and behavioural responses to intracerebroventricularly (i.c.v.) administered neuropeptide K (NPK) were studied in conscious rats. The central effects of NPK were characterized by pretreatment (i.c.v.) with selective antagonists for the NK1 ((+/-)-CP 96345 and RP 67580), NK2 (SR 48968) and NK3 (R 487) receptors. 2. NPK (10-65 pmol) induced tachycardia and dose-dependent increases of mean arterial blood pressure. The cardiovascular responses reached a maximum within 3 min post-injection and lasted for more than 1 h. Concurrently, NPK produced dose-dependent increases of face washing, head scratching, grooming, walking and wet dog shakes. 3. A desensitization of most of the behavioural responses (except head scratching) but not of the cardiovascular response was shown when two consecutive injections of 25 pmol NPK were given 24 h apart. 4. Both the cardiovascular and behavioural responses (except the head scratching) to 25 pmol NPK were blocked by pre-administration (i.c.v.) of 6.5 nmol (+/-)-CP 96345 or RP 67580 given 5 min earlier. No inhibition of NPK responses was observed when 6.5 nmol SR 48968 or R 487 were used in a similar study. Additionally, NPK effects were significantly reduced 24 h after the prior injection of (+/-)-CP 96345 but not of RP 67580. 5. These results support the involvement of NK1 receptors in the cardiovascular and behavioural effects of i.c.v. NPK. Thus, this peptide may play a putative role in central cardiovascular regulation as it is the most potent endogenous tachykinin described centrally, to date.

Animals↗
PubMed1993

Neuropeptide K potently stimulates the hydrolysis of phosphatidylinositol in the rat spinal cord.

The accumulation of total [3H]inositol phosphates stimulated by neuropeptide K was investigated in rat spinal cord slices and compared with that of substance P and carbachol. The rank order of potency of the agonists in stimulating [3H]phosphatidylinositol (PI) hydrolysis was neuropeptide K > substance P > carbachol. The PI responses to neuropeptide K and substance P were significantly (P < 0.01) enhanced when slices were incubated with a mixture of bacitracin (30 microM), captopril (10 microM) and leupeptin (2 micrograms/ml), yet the order of potency remained unchanged. These results show for the first time that NPK can stimulate the PI hydrolysis in the adult rat spinal cord. The relatively greater degree of potency and efficacy of NPK over SP to stimulate PI hydrolysis does not appear to be entirely attributed to the metabolic stability of the peptide.

Animals↗
PubMed1993

Use of non-peptide tachykinin receptor antagonists to substantiate the involvement of NK1 and NK2 receptors in a spinal nociceptive reflex in the rat.

Non-peptide antagonists of the NK1 and NK2 receptors were tested as inhibitors of the reaction time in the rat tail-flick and on the decrease of reaction time induced by the intrathecal injection of the NK1 receptor selective agonist [Sar9,Met(O2)11]SP or of the NK2 selective agonist NKA-(4-10). The decrease in reaction time produced by the NK1 agonist lasted less than 11 min while that evoked by the NK2 agonist persisted 26 min after injection. When given intrathecally, CP-96,345 and its chloro analog, Cl-CP, blocked dose-dependently both the behavioral responses and the decreases of reaction time induced by 6.5 nmol of [Sar9,Met(O2)11]SP while they failed to modify the hyperalgesic response to 6.5 nmol NKA-(4-10); CP-96,345 was found more potent than Cl-CP and was also active as an antagonist when given intravenously. In contrast, SR 48968 (6.5 and 65 nmol) blocked the NKA-(4-10)-induced decreases in reaction time and was inactive against the hyperalgesic effect of [Sar9,Met(O2)11]SP. The three antagonists blocked in a reversible manner, were inactive on their own on reaction time and non-toxic. The results indicate that the non-peptide CP-96,345 readily crosses the blood brain barrier and acts as a selective antagonist on spinal NK1 receptors, while SR 48968 is selective on NK2 receptors in the rat spinal cord. Hence, CP-96,345 and SR 48968 highlight a functional role of NK1 and NK2 receptors in spinal sensory neurotransmission.

Animals↗
PubMed1993

Autoradiographic localization of [125I-Tyr8]-bradykinin receptor binding sites in the guinea pig spinal cord.

The present study aimed to localize and characterize [125I-Tyr8]-BK binding sites in all major segments of the guinea pig spinal cord using in vitro quantitative receptor autoradiography. [125I-Tyr8]-BK specific binding sites were localized predominantly in superficial layers of the dorsal horn, with lamina II depicting the highest labelling. The density of specific binding in laminae I and III was moderate, whereas in other areas, i.e., laminae IV-X, lower amounts of labelling were noticed. The B2 receptor antagonists D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe 140), D-Arg[Hyp3,D-Phe7,Leu8]-BK, Tyr0,D-Arg[Hyp3,D-Phe7,Leu8]-BK, D-Arg[Tyr3,D-Phe7,Leu8]-BK, D-Arg[Hyp2,Thi5,8,D-Phe7]-BK, D-Arg[Hyp3,Leu8]-BK and D-Arg[Hyp3,Gly6,Leu8]-BK as well as unlabelled [Tyr8]-BK inhibited [125I-Tyr8]-BK binding with respective Ki values of 0.04, 12.4, 23.4, 34.5, 43.5, 33.5, 23.0, and 0.6 nM while B1 related molecules (Tyr0,des-Arg10-kallidin and [Leu8]-des-Arg9-BK) did not significantly inhibit [125I-Tyr8]-BK binding up to micromolar concentrations. These results indicate that the specific [125I-Tyr8]-BK binding sites present in the guinea pig spinal cord belong to the B2 receptor subtype. The high density of B2 binding sites in the substantia gelatinosa provides an anatomical evidence in favour of a role for BK as a modulator of nociceptive information.

Amino Acid Sequence↗
PubMed1993

Inhibitory action of (+/-)CP-96,345 on the cardiovascular responses to intrathecal substance P and neuropeptide K in the conscious freely moving rat.

(+/-)CP-96,345, a nonpeptide and highly selective NK-1 receptor antagonist, was tested acutely and chronically as an inhibitor of the cardiovascular responses induced by the intrathecal (i.t.) injection of substance P (SP) and neuropeptide K (NPK) in the conscious rat. When given at T-9 spinal cord level, NPK (0.65, 3.25 and 6.5 nmol) and SP (6.5, 16.25 and 32.5 nmol) produced increases in mean arterial pressure and heart rate. The cardiovascular responses to NPK were greater in intensity and duration than those produced by SP. The prior i.t. injection of (+/-)CP-96,345 (0.65 and 6.5 nmol, 15 min earlier) inhibited in a dose-dependent manner the pressor response and the tachycardia induced by 6.5 nmol SP while 65 nmol of the antagonist was required to reduce the effects of 3.25 nmol NPK. However, both the SP and NPK-induced cardiovascular changes were blocked 2 days after the i.t. injection of 6.5 nmol (+/-)CP-96,345. Five days after a single i.t. injection of 6.5 nmol (+/-)CP-96,345, the cardiovascular response to SP remained unaffected while that of NPK was partially attenuated. Moreover, (+/-)CP-96,345 was active as an antagonist when given i.v. at the dose of 0.13 mg/kg. Conversely, (+/-)CP-96,345 failed to block the cardiovascular effect caused by the i.t. injection of 81 pmol bradykinin and did not produce any changes on resting blood pressure and heart rate when given alone either i.t. or i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mediation by B1 and B2 receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs.

1. Vasodepressor responses to intravenous (i.v.) injection of bradykinin (BK) and des-Arg9-BK, a selective B1 kinin receptor agonist, were characterized following i.v. pretreatment with selective B1 ([Leu8]-des-Arg9-BK) and B2 (Hoe 140) kinin receptor antagonists in anaesthetized dogs. 2. Des-Arg9-BK (0.05-3.3 nmol kg-1) produced dose-dependent decreases in mean arterial blood pressure with a ED50 0.4 nmol kg-1. The vasodepressor effects evoked by des-Arg9-BK (0.6 nmol kg-1) and BK (0.2 nmol kg-1) were greater after i.v. and i.a. injections, respectively. 3. The vasodepressor response to BK (0.6 nmol kg-1) but not to des-Arg9-BK (0.6 nmol kg-1) was significantly (P < 0.001) blocked by pretreatment with the B2 receptor antagonist, Hoe 140. 4. The vasodepressor response to des-Arg9-BK (0.6 nmol kg-1) but not to BK (0.6 nmol kg-1) was significantly (P < 0.001) reduced by pretreatment with the selective B1 receptor antagonist, [Leu8]-des-Arg9-BK. Although both B1 and B2 receptor antagonists caused a transient fall in blood pressure, their inhibitory action was unlikely to be related to a desensitization mechanism. 5. Inhibition of prostaglandin synthesis with indomethacin prevented the vasodepressor response induced by arachidonic acid (1 mg kg-1, i.v.) but not that to BK or des-Arg9-BK (0.6 nmol kg-1). 6. These results suggest, firstly, that the vasodepressor responses to i.v. BK and des-Arg9-BK are mediated by the activation of B2 and B1 receptors, respectively; secondly, that prostaglandins are not involved in the vasodepressor responses to kinins.These findings provide pharmacological evidence for the existence of functionally active B1 receptors in canine cardiovascular homeostasis.

Anesthesia↗
PubMed1993

Cardiovascular effects of intrathecally administered bradykinin in the rat: characterization of receptors with antagonists.

1. The effects of intrathecal (i.t.) pretreatment with selective B1 or B2 kinin receptor antagonists were studied on the cardiovascular response to i.t. injection of bradykinin (BK) in conscious freely moving rats. 2. BK (81 pmol) produced an increase in mean arterial pressure (MAP: 9-13 mmHg) and decrease in heart rate (HR: 20-30 beats min-1) that reached a maximum 2 min after injection. 3. The BK-induced cardiovascular responses were dose-dependently and reversibly reduced by four antagonists with the following rank order of potency: Tyr, D-Arg[Hyp3,D-Phe7,Leu8]-BK = D-Arg[Tyr3,D-Phe7,Leu8]-BK = D- Arg[Hyp3,D-Phe7,Leu8]-BK > D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe 140). These compounds failed to alter the cardiovascular response to i.t. injection of 8.1 nmol of substance P. 4. Other compounds acting on the B2 receptor, namely D-Arg[Hyp3,Gly6,Leu8]-BK, D-Arg[Hyp3,D-Phe7]-BK, D-Arg[Hyp2,Thi5,8,D-Phe7]-BK and D-Arg[Hyp3,Gly6,D-Phe7,Leu8]-BK or on the B1 receptor, [Leu8]-desArg9-BK, did not influence the cardiovascular responses to BK at doses devoid of intrinsic activity on MAP and HR. 5. None of the kinin receptor antagonists caused motor impairment, respiratory arrest or persisting cardiovascular changes. 6. These results confirm that the cardiovascular effects induced by i.t. BK are mediated by the activation of a B2 receptor in the rat spinal cord. However, the rank order of potency of antagonists does not conform to the classical B2 functional site characterized in peripheral tissues.

Animals↗
PubMed1993

Spinal cord serotonin receptors in cardiovascular regulation and potentiation of the pressor response to intrathecal substance P after serotonin depletion.

The aim of this study was to characterize, in conscious rats, the spinal cord 5-hydroxytryptamine (5-HT) receptors involved in mean arterial pressure (MAP) and heart rate (HR) regulation as well as to examine the influence of bulbospinal 5-HT fibers on cardiovascular responses to intrathecal (i.t.) substance P (SP). The i.t. injection of 5-HT or 5-carboxamidotryptamine (5-CT) (5-HT1A,1B,1D agonist) reduced MAP and increased HR in a dose-dependent manner. In contrast, the agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 5-HT1A agonist) and alpha-CH3-5-HT (5-HT1C and 5-HT2) only caused a decrease in HR, while the agonist 2-CH3-5-HT (5-HT3) was devoid of cardiovascular effects. The vasodepressor response to 5-CT was antagonized by methiothepin but not affected by mesulergine, ketanserin, propranolol, or yohimbine. However, all five antagonists reduced the HR increase to 5-CT. Ketanserin, propranolol, mesulergine, yohimbine, and methylsergide were without effect on resting MAP, while methiothepin reduced MAP. Methiothepin, ketanserin, and methylsergide increased resting HR, yet the other antagonists had no effect on this parameter. Rats treated with p-chlorophenylalanine or 5,7-dihydroxytryptamine, but not with 6-hydroxydopamine, exhibited higher resting HR than that of control rats. Although the resting MAP was unaffected, the pressor response to i.t. SP was significantly enhanced by either 5-HT toxin. The results suggest that the receptor mediating the depressor response to 5-HT and 5-CT conforms with the broad pharmacological profile of a 5-HT1-like receptor and is unlikely to be of the 5-HT2 or 5-HT3 subtype. Since the HR response evoked by 5-CT was blocked by antagonists that exhibit affinities for various 5-HT receptor subtypes, it is suggested that a nonspecific blockade or, alternatively, that more than one receptor contributes to this cardiac effect. In addition, the results raise the possibility that a spinal 5-HT input, likely mediated by 5-HT2 receptors, tonically inhibits HR. Hence, an antagonistic interaction between 5-HT and SP is proposed to play a role in the control of arterial blood pressure in the spinal cord.

Animals↗
PubMed1993

In vivo B2-receptor-mediated negative chronotropic effect of bradykinin in canine sinus node.

The chronotropic response to bradykinin (BK) injected into the sinus node artery was evaluated in anesthetized dogs. The animals (n = 14) were vagotomized and pretreated with propranolol (1 mg/kg i.v.) to prevent baroreceptor-mediated effects. Dose-dependent decreases in heart rate (from 2.4 +/- 1.3% for 1 microgram of BK to 13.1 +/- 3.7% for 10 micrograms of BK), as well as a significant fall in systemic systolic and diastolic blood pressures, were observed. Captopril (2 mg/kg i.v.) caused significant decreases in systolic (from 117 +/- 11 to 77 +/- 12 mmHg, P < 0.001) and diastolic (from 87 +/- 8 to 52 +/- 8 mmHg, P < 0.001) blood pressures but had no effect on heart rate. Converting-enzyme inhibition potentiated the BK-induced bradycardia. The new potent B2-receptor antagonist, HOE 140 (100 micrograms), significantly blocked the BK-induced chronotropic effect, whereas desArg9-BK, a B1-receptor agonist, was without effect. Prostaglandin involvement was excluded, since pretreatment with indomethacin did not prevent the bradycardia. In conclusion, in vivo BK induces a direct negative chronotropic effect, which is potentiated by converting-enzyme inhibition and is mediated by the B2-receptors independently of the prostaglandins.

Adrenergic beta-Antagonists↗