Chronic administration of oxprenolol and metoprolol attenuate sympathetic cardiovascular responses only in non-adrenalectomized pithed rats

Background: Recently, novel corticotropin-releasing factor (CRF)-related peptides, named urocortin I (UcnI), UcnII, and UcnIII were described. Available data suggest that the Ucns are part of a peripheral CRF system modulating cardiovascular function and mediating cardiovascular responses to stress. Blood pressure (BP) lowering effects have been described after administration of UcnI. However, no data are available on effects of UcnII on BP in an animal model of systemic arterial hypertension. Methods: Experiments were performed in Dahl salt-sensitive (DSS) and salt-resistant rats (DSR, control). Animals were fed a diet containing 4% NaCl (high salt) to induce arterial hypertension in DSS rats. At the end of week 2 of high salt diet, both DSS and DSR rats were randomly assigned to i.p. injections of either UcnII (2.5 μg/kg body weight) or vehicle b.i.d. for five weeks. Animals underwent repetitive tail cuff BP measurements at baseline (prior to first injection), at 5 and 15 minutes after the first injection and at week 1, 2, and 5 of b.i.d. treatment. At week 5 animals were sacrificed to determine heart weight /body weight ratio. Results: Systolic BP (SBP, mmHg) and heart rate (HR, min −1 ) are given in the following table as mean ± SD (n=10 per group). Conclusions: In hypertensive DSS rats, acute CRF-receptor stimulation by UcnII immediately lowered BP to the range observed in DSR rats. Compared to vehicle-treated DSS rats, sustained BP reduction was observed with further chronic administration of UcnII. No severe reflex tachycardia was observed after administration of UcnII. Thus, CRF-receptor stimulation might represent a novel approach to the treatment of arterial hypertension.

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Blocking properties of terguride at the 5-HT2 receptor subtypes mediating cardiovascular responses in the rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0591 ◽

2020 ◽

Vol 98 (8) ◽

pp. 511-521

Author(s):

Oscar Alcántara-Vázquez ◽

Ma. Trinidad Villamil-Hernández ◽

Araceli Sánchez-López ◽

Heinz H. Pertz ◽

Carlos M. Villalón ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Diastolic Blood Pressure ◽

Receptor Agonist ◽

Cardiovascular Responses ◽

Receptor Subtypes ◽

Pithed Rats ◽

Anaesthetized Rats ◽

Dose Dependent

In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT2A/2B receptors. This study has now investigated terguride’s blocking properties on central/peripheral 5-HT2 receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.v. administration of several compounds. In both groups of rats, i.v. bolus injections of 5-HT or (±)-DOI (a 5-HT2 receptor agonist; 1–1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and heart rate. These responses were dose-dependently antagonized by terguride (10–3000 μg/kg). In anaesthetized rats, i.v. bolus injections of BW723C86 (a 5-HT2B receptor agonist; 1–1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and not dose-dependent increases in heart rate, while in pithed rats, these responses were attenuated. The vasopressor responses elicited by BW723C86 in anaesthetized rats were dose-dependently blocked by terguride (10–300 μg/kg), whereas its the tachycardic responses were dose-independently blocked. These results, taken together, suggest that terguride behaved as an antagonist at the 5-HT2 receptors located in the central nervous system and (or) the systemic vasculature. This is the first evidence demonstrating that terguride can block central/peripheral 5-HT2 receptors mediating cardiovascular responses in anaesthetized or pithed rats.

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Evaluation of the Cardiovascular Responses in Nicotinamide+Streptozotocin Diabetic Pithed Rats

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.627.6 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

David Centurion ◽

Miriam Torres‐Gutierrez ◽

Erika Gutierrez‐Lara ◽

Araceli Sanchez‐Lopez

Keyword(s):

Cardiovascular Responses ◽

Pithed Rats

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Alteration of adrenergic responses by chronic cholinergic blockade

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1960.199.1.117 ◽

1960 ◽

Vol 199 (1) ◽

pp. 117-123

Author(s):

David C. Jerram

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cardiac Output ◽

Diastolic Blood Pressure ◽

Peripheral Resistance ◽

Submaxillary Gland ◽

Chronic Administration ◽

Cardiovascular Responses ◽

Adrenergic Agents ◽

Cholinergic Blockade

The effect of the chronic administration of cholinergic blocking agents on the secretory and cardiovascular responses to epinephrine, levarterenol and isoproterenol has been determined in the dog. Chronic cholinergic blockade (CCB) produced a supersensitivity of the submaxillary gland to epinephrine and levarterenol as has been shown previously. Isoproterenol was found to have a profound secretory effect on the submaxillary gland of the dog. During CCB, the volume of secretion produced by isoproterenol was greatly increased. Changes in systolic and diastolic blood pressure, cardiac output, peripheral resistance, heart rate and duration of systole produced by graded doses of epinephrine, levarterenol and isoproterenol were not significantly or systematically altered by CCB. It was concluded that CCB does not alter the sensitivity of the vasculature to adrenergic agents. In 12 of 13 dogs, the heart rate after acute atropinization was significantly lower during CCB than in the control experiments.

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CHRONIC ADMINISTRATION OF CALCIUM ENTRY BLOCKERS AND THE CARDIOVASCULAR RESPONSES TO HIGH DOSES OF FENTANYL IN MAN

Anesthesiology ◽

10.1097/00000542-198209001-00295 ◽

1982 ◽

Vol 57 (3) ◽

pp. A295-A295 ◽

Cited By ~ 11

Author(s):

Edmond S. Freis ◽

Demetrios G. Lappas

Keyword(s):

Chronic Administration ◽

Cardiovascular Responses ◽

Calcium Entry ◽

Calcium Entry Blockers ◽

High Doses

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Hypertension during chronic peripheral and central infusion of angiotensin III

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.249.2.e201 ◽

1985 ◽

Vol 249 (2) ◽

pp. E201-E208 ◽

Cited By ~ 2

Author(s):

G. D. Fink ◽

C. A. Bruner

Keyword(s):

Intravenous Infusion ◽

Pressor Response ◽

Parent Compound ◽

Chronic Administration ◽

Blood Levels ◽

Chronic Hypertension ◽

Electrolyte Balance ◽

Ang Ii ◽

Potency Ratio ◽

Pithed Rats

Recent studies have suggested that the angiotensin II (ANG II) metabolite [Des-Asp]ANG II (ANG III) may be nearly equipotent with the parent compound in causing several acute neural responses known to be stimulated by angiotensin peptides (i.e., drinking, augmentation of sympathetic neurotransmission, and centrally mediated pressor responses). Because neural actions of ANG II are thought to contribute importantly to the ability of this hormone to cause chronic hypertension, the purpose of the present experiments was to explore the cardiovascular effects of chronic administration of ANG III either into the bloodstream or directly into the brain via the cerebral ventricles. The neurogenic component of the pressor response to acute infusion of ANG III also was reinvestigated. In anesthetized pithed rats (n = 6) ANG III had only 10% of the pressor potency of ANG II when given by acute (5-10 min) intravenous infusion. In conscious rats (n = 5) ANG III had 25% of the pressor potency of ANG II when tested using acute intravenous administration. The acute intravenous pressor potency ratio in conscious versus pithed rats was 4.8 for ANG III and 1.1 for ANG II, suggesting that, compared with ANG II, the pressor response to ANG III shows a greater dependence on neurogenic mechanisms at the doses tested. Chronic (5-day) intravenous infusion of ANG III (at 10, 20, and 100 ng/min) caused sustained hypertension without changes in fluid/electrolyte balance, but only at a dose (100 ng/min) estimated to produce blood levels of ANG III well beyond the "physiological" range.(ABSTRACT TRUNCATED AT 250 WORDS)

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Age-related changes in thirst, salt appetite, and arterial blood pressure in response to aldosterone-dexamethasone combination in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00490.2014 ◽

2015 ◽

Vol 308 (10) ◽

pp. R807-R815 ◽

Cited By ~ 3

Author(s):

Robert L. Thunhorst ◽

Baojian Xue ◽

Terry G. Beltz ◽

Alan Kim Johnson

Keyword(s):

Blood Pressure ◽

Sodium Intake ◽

Chronic Administration ◽

Cardiovascular Responses ◽

Brown Norway ◽

Salt Appetite ◽

Arterial Blood ◽

Age Related ◽

Sodium Ingestion ◽

Old Rats

This work examined the effects of age on daily water and sodium ingestion and cardiovascular responses to chronic administration of the mineralocorticoid, aldosterone (ALDO) either alone or together with the glucocorticoid, dexamethasone (DEX). Young (4 mo), adult (12 mo), and aged (30 mo) male Brown Norway rats were prepared for continuous telemetry recording of blood pressure (BP) and heart rate (HR). Baseline water and sodium (i.e., 0.3 M NaCl) intake, BP, and HR were established for 10 days. Then ALDO (60 μg/day sc) was infused alone, or together with DEX (2.5 or 20 μg/day sc), for another 10 days. Compared with baseline levels, ALDO stimulated comparable increases in daily saline intake at all ages. ALDO together with the higher dose of DEX (i.e., ALDO/DEX20) increased daily saline intake more than did ALDO, but less so in aged rats. Infusion of ALDO/DEX20 increased mean arterial pressure (MAP), and decreased HR, more than did infusion of ALDO. The changes in MAP in response to both treatments depended on age. For all ages, MAP and saline intake increased simultaneously during ALDO, while MAP always increased before saline intake did during ALDO/DEX20. Contrary to our predictions, MAP did not increase more in old rats in response to either treatment. We speculate that age-related declines in cardiovascular responses to glucocorticoids contributed to the attenuated increases in sodium intake in response to glucocorticoids that were observed in older animals.

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