ACUTE AND CHRONIC INFLUENCE OF DIAZOXIDE ON ADRENAL-REGENERATION HYPERTENSION

The antihypertensive activity of diazoxide was evaluated in rats with regenerating adrenal glands. The drug was given chronically in the drinking fluid, and also by subcutaneous injection at two intervals during the experiment. For a brief period diazoxide in the drinking fluid was replaced by hydrochlorothiazide. Diazoxide caused detectable sodium retention, despite which it reduced the intensity of hypertension and reduced the incidence, severity, and extent of the accompanying vascular lesions. The substitution of hydrochlorothiazide for diazoxide, or the subcutaneous administration of diazoxide to rats that were then consuming it in the drinking fluid, usually further depressed the blood pressure. It may thus be concluded that maximal blood pressure lowering effects of diazoxide were not achieved by oral ingestion, and that while the drug does afford a significant degree of protection against adrenal-regeneration hypertension it is less effective in this respect than hydrochlorothiazide, possibly because diazoxide causes sodium retention whereas hydrochlorothiazide promotes saluresis.

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Long-term blood pressure lowering and cGMP-activating actions of the novel ANP analog MANP

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00354.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. R669-R676 ◽

Cited By ~ 1

Author(s):

Yang Chen ◽

Jacob J. Schaefer ◽

Seethalakshmi R. Iyer ◽

Gerald E. Harders ◽

Shuchong Pan ◽

...

Keyword(s):

Blood Pressure ◽

Subcutaneous Injection ◽

Ex Vivo ◽

Subcutaneous Administration ◽

Therapeutic Drug ◽

Hypertensive Rats ◽

Pressure Lowering ◽

Intracellular Ca ◽

Isolated Arteries

Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analog currently entering clinical trials for hypertension. Previous reports demonstrate that this analog MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared with ANP; thus, it may represent a new therapeutic drug for hypertension. A major goal of this study was to establish that chronic subcutaneous delivery of MANP is feasible and hypotensive together with cGMP effects. We investigated the BP-lowering and cGMP-activating actions of acute and chronic subcutaneous delivery in normal and hypertensive rats. Furthermore, we explored vascular mechanisms of MANP in human aortic smooth muscle cells (HASMC) and ex vivo in isolated arteries. In normal rats with a single subcutaneous injection, MANP promoted robust dose-dependent BP-lowering actions and natriuresis, together with cGMP activation. Most importantly in hypertensive rats, once-a-day subcutaneous injection of MANP for 7 days induced cGMP elevation and long-term BP reduction compared with vehicle. Mechanistically, in HASMC, MANP activated cGMP and attenuated angiotensin II-mediated increases in intracellular Ca2+ levels while directly vasorelaxing arterial rings. Our study demonstrates for the first time the effectiveness of subcutaneous administration of MANP for 7 days and provides innovative, vascular mechanisms of BP regulation supporting its continued development as a novel therapeutic for hypertension.

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Comparative Anti-Hypertensive Effectiveness of β-Adrenoreceptor Antagonists with Different Pharmacological Properties: Dose—Response Studies during Acute and Chronic Administration

Clinical Science ◽

10.1042/cs051541s ◽

1976 ◽

Vol 51 (s3) ◽

pp. 541s-544s

Author(s):

S. H. Taylor ◽

C. Davidson ◽

W. Singleton ◽

U. Thadani

Keyword(s):

Blood Pressure ◽

Common Property ◽

Diastolic Pressure ◽

Systolic Pressure ◽

Antihypertensive Activity ◽

Pharmacological Properties ◽

Blood Pressure Lowering ◽

Double Blind ◽

Pressure Lowering ◽

Lowering Activity

1. Immediate and long-term blood pressure-lowering activity of five β-adrenoreceptor antagonists with different ancillary pharmacological properties were compared in a randomized double-blind placebo controlled factorial trial in twenty-five previously untreated patients with stable uncomplicated essential hypertension. 2. In doses which produced similar reductions in exercise tachycardia, all drugs exerted similar antihypertensive activity, which was greater on systolic than diastolic pressure and greatest during exercise. 3. These effects were maximum within an hour and lasted for over 8 h after a single oral dose. 4. Blood pressure-lowering activity, particularly the reduction in exercise systolic pressure, was significantly related to the logarithm of the dose of each drug. 5. Anti-hypertensive activity was maximally enhanced after 4 weeks of sustained treatment at any given dose. There was no short-term habituation to treatment and substitution with placebo resulted in a return of the blood pressure to pretreatment values within 4 weeks without subsequent overshoot. 6. The blood pressure-lowering activity of these drugs was predominantly related to their common property of competitive antagonism of cardiac β-adrenoreceptors; their ancillary pharmacological properties, with the exception of intrinsic vasodilator activity, played little part in this response.

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Effect of Eleutherine americana Merr. bulb extract on blood pressure and heart rate in anesthetized hypertensive rats

Jurnal Sains Farmasi & Klinis ◽

10.25077/jsfk.5.2.119-125.2018 ◽

2018 ◽

Vol 5 (2) ◽

pp. 119

Author(s):

Yori Yuliandra ◽

Rizki Oktarini ◽

Armenia Armenia

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Saline Solution ◽

Ethanolic Extract ◽

Male Rats ◽

Antihypertensive Activity ◽

Sprague Dawley ◽

Blood Pressure Lowering Effect ◽

Pressure Lowering ◽

Eleutherine Americana

The effect of ethanolic extract of Eleutherine americana Merr. on the blood pressure and heart rate has been investigated. A number of 25 Sprague-Dawley male rats were induced with prednisone 1.5 mg/kg in combination with saline solution 2.5% for 14 days to obtain hypertension model. The rats were anesthetized and prepared for the recording of blood pressure and heart rate. The rats were divided into five groups receiving 100, 200, and 400 mg/kg of the extract, vehicle control, and captopril 30 mg/kg as the reference. The treatment was administered three times with 30 minutes interval. The systolic (SBP), diastolic (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. The data were analyzed with two-way analysis of variance (ANOVA) followed by Duncan’s MRT (95% confidence interval). The study revealed that the extract exhibited a blood pressure lowering effect. The best antihypertensive activity of the extract was shown by the dose of 100 mg/kg. Meanwhile, HR was also affected inversely by the treatment, in which the lowest dose caused the highest increase. The study suggests that the extract of Eleutherine americana exhibits antihypertensive activity that may be potential for future development of drugs.

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