Spinal actions of substance P analogues on cardiovascular responses in the rat: a structure–activity analysis

1987 ◽  
Vol 65 (3) ◽  
pp. 412-418 ◽  
Author(s):  
Réjean Couture ◽  
Alka Gupta ◽  
René Kérouac ◽  
Emanuel Escher ◽  
Domenico Regoli
Keyword(s):  
Heart Rate ◽  
Amino Acid ◽  
Mean Arterial Pressure ◽  
Substance P ◽  
Arterial Pressure ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Hypotensive Effect ◽  
Intrathecal Administration ◽  
Substance P Analogues

Ten substance P (SP) analogues were tested for their effects on mean arterial pressure and heart rate following intrathecal administration in the pentobarbital anaesthetized rat. The 10 analogues are [D-Pro4,D-αNpa7,9,10]SP(4–11) (A-I),(D-αNpa7,9,10]Sp (A-II);[D-Trp7,9,10]SP (A-III),[D-Pro4,D-Npa7,9, Phe11]SP(4–11) (A-IV),D-Pro4, D-βNpa7,D-αNpa9,D-Phe11]SP(4–11) (A-V), [D-Pro4,Lys6,D-Trp7,9,10, Phe11]SP(4–11) (A-VII),[D-Pro4,D-Trp7,9,10,Phe11]SP(4–11) (A-X),[D-Pro4,D-Trp7,9,10, Trp11]SP(4–11) (A-VIII),[D-Trp7,9,10, Trp11]SP (A-IX), and [D-Pro4,D-Phe7,9,10, Phe11]SP(4–11) (A-X). At 6.5 nmol, the analogues containing the amino acid D-Npa (A-I, A-II, A-IV, and A-V) or D-Phe (A-X) in positions 7, 9, or 10 or SP or its C-terminal octapeptide are devoid of the long-lasting cardio- and vaso-depressor effects, which are otherwise seen with analogues containing the amino acid D-Trp (A-III, A-VI, A-VII, A-VIII, and A-IX) in the same positions. Some of the analogues containing D-Npa maintain the initial hypotensive effect seen with SP while the analogue containing D-Phe produces only a small hypertensive response. The 10 analogues when tested at a dose that failed to alter basal mean arterial pressure and heart rate did not block the cardiovascular responses elicited by SP and no cross desensitization was observed between SP and these analogues. It appears that these SP analogues exert cardiovascular effects in the rat spinal cord probably without interacting with SP receptors.

Spinal action of neurokinins in the rat: effects on mean arterial pressure, heart rate, and vascular permeability

1987 ◽  
Vol 65 (11) ◽  
pp. 2182-2187 ◽  
Author(s):  
Harout Hasséssian ◽  
Réjean Couture ◽  
Line Jacques
Keyword(s):  
Spinal Cord ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Vascular Permeability ◽  
Cardiovascular Responses ◽  
Intrathecal Administration ◽  
Water Soluble ◽  
Neurokinin A ◽  
Anaesthetized Rats

In urethane-anaesthetized rats, the intrathecal administration of 6.5 nmol of substance P (SP), neurokinin A (NKA), or neurokinin B (NKB) at the T8–T10 level of the spinal cord enhances mean arterial pressure and heart rate. However, in the pentobarbital-anaesthetized rat, while NKB produces no effect on mean arterial pressure, NKA produces a biphasic change and SP, a depressor response. All three neurokinins elicit a tachycardia. The following rank order of potency SP ≥ NKA > NKB is observed in relation to these cardiovascular responses when either one of the two anaesthetics is used. The low cardiovascular activity of NKB cannot be attributed to its hydrophobicity, as the water soluble analogue of NKB, [Arg0] NKB, elicits a response as weak as the native peptide. In pentobarbital-anaesthetized rats, the intrathecal administration of 6.5 nmol of SP, also enhances plasma protein extravasation in cutaneous tissues of the back, the hind paws, and the ears. In this response NKA and NKB are either inactive (skin of hind paws) or less potent than SP (ears and dorsal skin). These findings agree with the hypothesis that in the rat spinal cord, the neurokinin receptor producing changes in mean arterial pressure, heart rate, and vascular permeability is of the NK-1 subtype.

Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens

2004 ◽  
Vol 286 (1) ◽  
pp. R138-R142 ◽  
Author(s):  
Ulrich Nordheim ◽  
Karl G. Hofbauer
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
High Fat Diet ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Chow Diet ◽  
High Fat ◽  
Standard Chow Diet ◽  
Ad Libitum

In the present experiments the gut hormone peptide YY3-36 (PYY3-36), which inhibits neuropeptide Y (NPY) release, was used as a tool to study the cardiovascular effects of endogenous NPY under different dietary regimens in rats instrumented with a telemetry transmitter. In a first experiment, rats were placed on a standard chow diet ad libitum and in a second experiment on a high-fat diet ad libitum. After 6 wk, PYY3-36 (300 μg/kg) or vehicle was injected intraperitoneally. In a third experiment, PYY3-36 or vehicle was administered after 14 days of 50% restriction of a standard chow diet. In food-restricted rats, PYY3-36 increased mean arterial pressure (7 ± 1 mmHg, mean ± SE, P < 0.001 vs. saline, 1-way repeated-measures ANOVA with Bonferroni t-test) and heart rate (22 ± 4 beats/min, P < 0.001) during 3 h after administration. Conversely, PYY3-36 did not influence mean arterial pressure (0 ± 1 mmHg) and heart rate (-8 ± 5 beats/min) significantly in rats on a high-fat diet. Rats fed standard chow diet ad libitum showed an intermediate response (mean arterial pressure 4 ± 1 mmHg, P < 0.05, and heart rate 5 ± 2 beats/min, not significant). Thus, in our studies, divergent cardiovascular responses to PYY3-36 were observed in rats on different dietary regimens. These findings suggest that the cardiovascular effects of PYY3-36 depend on the hypothalamic NPY release, which is increased after chronic food restriction and decreased during a high-fat diet.

Naturally occurring hypertension in New World nonhuman primates: potential role of the perifornical hypothalamus

2007 ◽  
Vol 292 (2) ◽  
pp. R937-R945 ◽  
Author(s):  
Orville A. Smith ◽  
Cliff A. Astley
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
New World ◽  
Critical Role ◽  
Cardiovascular Responses ◽  
Routine Laboratory ◽  
New World Primates ◽  
Naturally Occurring

Hypertension is a prominent underlying factor in the genesis of cardiovascular-related morbidity and mortality. A major impediment to the investigation into the causes of the disease is the paucity of naturally occurring animal models of the disease. There is evidence that some species of New World primates spontaneously become hypertensive. We used chronically implanted pressure transducers to assess normally occurring blood pressure and heart rate levels at rest and during routine laboratory procedures in a group of one of these New World primates ( Aotus sp.). Resting mean arterial pressure ranged from 72 to 130 mmHg. Three animals were judged to have resting mean arterial pressure levels in the hypertensive range (≥110 mmHg). In all of the animals, pressor responses to routine laboratory events were exaggerated (average highest mean pressure during 1 min from any session was 97–196 mmHg). Subsequently, the region of the perifornical/lateral hypothalamus known to produce elevated blood pressure and heart rate responses to electrical stimulation was removed, and the blood pressure responses to the laboratory routines were significantly decreased and, in some cases, eliminated. Control lesions in nearby tissue had no effect on these responses. This region may play a critical role in initiating or exacerbating cardiovascular responses that contribute to the development of essential hypertension.

Neuronal and cardiovascular responses to ANF microinjected into the solitary nucleus

1989 ◽  
Vol 256 (2) ◽  
pp. R577-R582 ◽  
Author(s):  
R. Ermirio ◽  
P. Ruggeri ◽  
C. E. Cogo ◽  
C. Molinari ◽  
F. R. Calaresu
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Unit Activity ◽  
Atrial Natriuretic Factor ◽  
Single Unit ◽  
Cardiovascular Responses ◽  
Firing Frequency ◽  
Neuronal Firing ◽  
Single Unit Activity

The effect on single-unit activity, arterial pressure, and heart rate of a microinjection of atrial natriuretic factor (ANF) into 78 histologically verified sites in the nucleus tractus solitarii (NTS) was investigated in rats. Injections of 50 nl of 10(-7) M ANF excited 34 neurons (44%), mainly localized at the level of the obex, inhibited 15 (19%), and had no effect on the remaining 29 (37%). The increase in firing frequency of the 34 excited neurons was always followed by a decline in mean arterial pressure [MAP, -10.6 +/- 1.8 (SE) mmHg; P less than 0.01] and heart rate [HR, -9.6 +/- 3.1 (SE) beats/min; P less than 0.05]. When injections of ANF caused either no effect or inhibition of single-unit activity, no changes in either MAP or HR were observed. Single units excited by injections of ANF were also excited by activation of arterial baroreceptors and inhibited by baroreceptor unloading. Control injections of an inactive peptide analogue of ANF or of vehicle never produced any effects on neuronal firing frequency or on MAP and HR. Similar results were obtained from animals paralyzed and artificially ventilated. These results support the hypothesis that ANF plays a role in the chemical transmission of baroreceptor information within the NTS.

Maternal responses to long-term hypoxemia in sheep

1989 ◽  
Vol 256 (6) ◽  
pp. R1340-R1347 ◽  
Author(s):  
T. Kitanaka ◽  
R. D. Gilbert ◽  
L. D. Longo
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Cardiovascular Responses ◽  
Uterine Blood Flow ◽  
O2 Uptake ◽  
Arterial Po2

To determine the maternal cardiovascular responses to long-term hypoxemia, we studied three groups of animals: 1) pregnant ewes (n = 20) at 110-115 days gestation subjected to hypoxia for up to 28 days; 2) pregnant ewes (n = 4) that served as normoxic controls; and 3) nonpregnant ewes (n = 6) subjected to hypoxemia for up to 28 days. We measured mean arterial pressure, heart rate, uterine blood flow, and uterine vascular resistance continuously for 1 h/day while the ewe was exposed to an inspired O2 fraction of 12-13% for at least 17 days. Arterial PO2, O2 saturation, hemoglobin, arteriovenous O2 difference, and uterine O2 uptake were measured daily while blood volume and erythropoietin concentration were measured weekly. In the pregnant hypoxic group arterial PO2 decreased from a control value of 101.5 +/- 5.1 to 59.2 +/- 5.1 Torr within a few minutes, where it remained throughout the study. The hemoglobin concentration increased from 8.9 +/- 0.5 to 10.0 +/- 0.5 g/dl within 24 h where it remained, whereas erythropoietin concentration increased from 16.6 +/- 2.1 to 39.1 +/- 7.8 mU/ml at 24 h but then returned to near-control levels. Arterial glucose concentration, mean arterial pressure, and cardiac output decreased slightly but insignificantly. In contrast, body weight, heart rate, blood volume, uterine blood flow, uterine O2 flow, uteroplacental O2 uptake, and the concentrations of catecholamines and cortisol remained relatively constant. Thus both pregnant and nonpregnant sheep experience relatively minor cardiovascular and hematologic responses in response to long-term hypoxemia of moderate severity.

Differential cardiovascular effects of central clonidine and B-HT 920 in conscious rats

1988 ◽  
Vol 66 (11) ◽  
pp. 1455-1460 ◽  
Author(s):  
Kathryn A. King ◽  
Catherine C. Y. Pang
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Plasma Concentrations ◽  
Cardiovascular Effects ◽  
Plasma Noradrenaline ◽  
Adrenoceptor Agonists ◽  
Noradrenaline And Adrenaline ◽  
Prior Administration

The effect of intracerebroventricular (i.c.v.) injection of the α2-adrenoceptor agonists clonidine and B-HT 920 on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of noradrenaline and adrenaline was examined in conscious unrestrained rats. The injection of 1.0 μg clonidine significantly decreased MAP and slightly decreased HR. Plasma noradrenaline and adrenaline levels were slightly but not significantly decreased after the injection of 1 μg clonidine. In contrast, the injection of 0.1–10.0 μg B-HT 920 increased MAP and decreased HR. Plasma noradrenaline and adrenaline levels were slightly increased after the injection of the 1- and 10-μg doses. The i.c. v. injection of the α2-antagonist rauwolscine slightly but not significantly increased MAP and plasma noradrenaline and adrenaline levels. The responses to i.c. v. injection of clonidine and B-HT 920 were not changed by prior administration of rauwolscine. Neither the pressor response to B-HT 920 nor the depressor response to clonidine was abolished by rauwolscine, suggesting that neither response was mediated by α2-adrenoceptors.

Hemodynamic effects of neurohypophyseal peptides with antidiuretic activity in dogs

1985 ◽  
Vol 249 (5) ◽  
pp. H1001-H1008 ◽  
Author(s):  
J. Schwartz ◽  
J. F. Liard ◽  
C. Ott ◽  
A. W. Cowley
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Peripheral Resistance ◽  
Cardiovascular Effects ◽  
Plasma Renin ◽  
Hemodynamic Effects ◽  
Antidiuretic Activity

Arginine vasopressin (AVP) is known to produce increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) and decreases in heart rate (HR), cardiac output (CO), and plasma renin activity (PRA). Some recent observations with AVP and synthetic analogues have suggested that under certain conditions, AVP can induce cardiovascular and reninsecretory responses in the opposite directions. To characterize the receptors mediating these responses, the effects of AVP, oxytocin, and synthetic neurohypophyseal analogues with specific antidiuretic, vasoconstrictor, or oxytocic activities were studied in conscious dogs. AVP and 2-phenylalanine-8-ornithine-oxytocin (Phe2Orn8OT, a selective vasoconstrictor agonist) produced similar responses when infused at 10 ng X kg-1 X min-1. That is, TPR and MAP increased, and CO, HR, and PRA decreased. Pretreatment with a selective vasoconstrictor antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid) 2-(O-methyl)tyrosine]AVP, abbreviated d(CH2)5Tyr(Me)-AVP (10 micrograms/kg), blocked the actions of Phe2Orn8OT. However, in the presence of d(CH2)5Tyr(Me)AVP, AVP actually decreased TPR and increased CO, HR, and PRA. An analogue with selective antidiuretic activity, 4-valine-8-D-AVP (VDAVP, 10 ng X kg-1 X min-1), produced the same effects as the combination of vasopressin plus d(CH2)5Tyr(Me)AVP. Neither the effects of VDAVP nor of AVP plus antagonist were blocked by propranolol (1 mg/kg). These data indicate that vasopressin, by its antidiuretic activity, produces cardiovascular effects that are opposite to many of those produced by its vasoconstrictor action and that these effects are not dependent on mediation by beta-adrenoceptors.

Cardiovascular responses to intrathecal vasopressin in conscious and anesthesized rats

1989 ◽  
Vol 256 (1) ◽  
pp. R193-R200 ◽  
Author(s):  
A. Martinez-Arizala ◽  
J. W. Holaday ◽  
J. B. Long
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Intrathecal Administration ◽  
Motor Dysfunction ◽  
Sprague Dawley ◽  
Cardiovascular Changes ◽  
Conscious Rats

Increases in mean arterial pressure and heart rate have been documented after the intrathecal administration of [Arg8]vasopressin (AVP) in rats. Prior studies in our laboratories with conscious rats indicated that these cardiovascular changes were associated with a marked hindlimb sensorimotor dysfunction. In this study, which represents the first systematic comparison of the effects of intrathecal AVP in conscious and anesthesized rats, we demonstrate that in conscious male Sprague-Dawley rats 1) the motor dysfunction induced by intrathecal AVP is accompanied by a rise in mean arterial pressure that is significantly greater than that produced by an equal intravenous dose of AVP, and 2) both paralytic and pressor effects of intrathecal but not intravenous AVP are blocked by the intrathecal administration of the V1-receptor antagonist d(CH2)5[Tyr(Me)2]AVP (V1-ANT) but are not blocked by intravenous phenoxybenzamine, hexamethonium, or [Sar1, Thr8]angiotensin II, an angiotensin II antagonist. In contrast, in anesthesized rats the arterial pressor response to intrathecal AVP was blocked by intrathecal V1-ANT, intravenous hexamethonium, and intravenous phenoxybenzamine. Furthermore, conscious but not anesthesized rats exhibited a tachyphylaxis to intrathecal AVP. These results indicate that intrathecal AVP produces both the cardiovascular changes and the sensorimotor deficits through interactions with centrally located V1-receptors. In addition, sympathetic catecholaminergic mechanisms mediate the rise in mean arterial pressure produced by intrathecal AVP in anesthesized rats, but they do not in conscious rats.

scholarly journals Abnormal cardiovascular response to nitroglycerin in migraine

Cephalalgia ◽  
2019 ◽  
Vol 40 (3) ◽  
pp. 266-277
Author(s):  
Willebrordus PJ van Oosterhout ◽  
Guus G Schoonman ◽  
Dirk P Saal ◽  
Roland D Thijs ◽  
Michel D Ferrari ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Stroke Volume ◽  
Total Peripheral Resistance ◽  
Cardiovascular Response ◽  
Peripheral Resistance ◽  
Cardiovascular Responses ◽  
Initial Increase

Introduction Migraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine. Methods In 16 women with migraine without aura and 10 age- and gender-matched controls without headache, intravenous nitroglycerin (0.5 µg·kg−1·min−1) was administered. Finger photoplethysmography continuously assessed cardiovascular parameters (mean arterial pressure, heart rate, cardiac output, stroke volume and total peripheral resistance) before, during and after nitroglycerin infusion. Results Nitroglycerin provoked a migraine-like attack in 13/16 (81.2%) migraineurs but not in controls ( p = .0001). No syncope was provoked. Migraineurs who later developed a migraine-like attack showed different responses in all parameters vs. controls (all p < .001): The decreases in cardiac output and stroke volume were more rapid and longer lasting, heart rate increased, mean arterial pressure and total peripheral resistance were higher and decreased steeply after an initial increase. Discussion Migraineurs who developed a migraine-like attack in response to nitroglycerin showed stronger systemic cardiovascular responses compared to non-headache controls. The stronger systemic cardiovascular responses in migraine suggest increased systemic sensitivity to vasodilators, possibly due to insufficient autonomic compensatory mechanisms.

scholarly journals Glucocorticoids act in the dorsal hindbrain to increase arterial pressure

2004 ◽  
Vol 286 (1) ◽  
pp. H458-H467 ◽  
Author(s):  
Deborah A. Scheuer ◽  
Andrea G. Bechtold ◽  
Sylvan S. Shank ◽  
Susan F. Akana
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glucocorticoid Receptors ◽  
Cardiovascular Effects ◽  
Systemic Circulation ◽  
Dorsal Hindbrain ◽  
Regulation Of Blood Pressure ◽  
Experimental Strategies

Glucocorticoid receptors (GRs) are present at a high density in the nucleus of the solitary tract (NTS), an area of the dorsal hindbrain (DHB) that is critical for blood pressure regulation. However, whether these receptors play any role in the regulation of blood pressure is unknown. We tested the hypothesis that glucocorticoids act in the DHB to increase arterial pressure using two experimental strategies. In one approach, we implanted pellets of corticosterone (Cort) or sham pellets onto the DHB over the NTS. Compared with rats with sham pellets, rats with DHB Cort pellets had an increased ( P < 0.05) mean arterial pressure (111 ± 2 vs. 104 ± 1 mmHg) and heart rate (355 ± 9 vs. 326 ± 5 beats/min) after 4 days. In the second approach, we implanted subcutaneous Cort pellets to increase the systemic Cort concentration and then subsequently implanted pellets of the GR antagonist mifepristone (Mif; previously RU-38486) or sham pellets onto the DHB. Two days of DHB Mif treatment reduced ( P < 0.05) mean arterial pressure in those rats with elevated plasma Cort levels (118 ± 2 vs. 108 ± 1 mmHg for sham vs. Mif DHB pellets). Cort and Mif pellets placed on the dura had no effects on arterial pressure or heart rate, ruling out systemic cardiovascular effects of the steroids. DHB Cort treatment had no effects on plasma Cort concentration or adrenal weight, indicating that the contents of the DHB Cort pellet did not diffuse into the systemic circulation or into the forebrain areas that regulate plasma Cort concentration in concentrations sufficient to produce physiological effects. Immunohistochemistry for the occupied GRs demonstrated that the Cort and Mif from the DHB pellets were delivered to the DHB with minimal diffusion to the ventral hindbrain or forebrain. We conclude that glucocorticoids act in the DHB to increase arterial pressure.

Sign in / Sign up

Export Citation Format

Share Document