Hypotensive effects of sodium volume depletion and 1-sar-8-ala-angiotensin II in relation to plasma renin in hypertensive patients

1977 ◽  
Vol 12 (1) ◽  
pp. 1-5 ◽  
Author(s):  
R. Fagard ◽  
A. Amery ◽  
P. Lijnen ◽  
T. Reybrouck
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin ◽  
Volume Depletion ◽  
Hypertensive Patients

Change in the Renin Dependency of Blood Pressure Induced by Volume Depletion and/or Propranolol Therapy in Hypertensive Patients

1976 ◽  
Vol 51 (s3) ◽  
pp. 189s-192s
Author(s):  
G. G. Geyskes ◽  
P. Boer ◽  
J. Vos ◽  
E. J. Dorhout Mees
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin ◽  
Special Importance ◽  
Volume Depletion ◽  
Blood Pressure Elevation ◽  
Hypertensive Patients ◽  
Angiotensin Ii Antagonist ◽  
Different Types ◽  
Propranolol Therapy

1. Plasma renin activity (PRA) and renin dependency of the blood pressure was analysed in ten patients with various forms of hypertension before and during treatment with volume depletion and/or propranolol. Renin dependency was tested by infusion of the specific competitive angiotensin II antagonist Sar1-Ala8-angiotensin II (P113). 2. The P113-induced fall of the blood pressure did correlate with the log PRA (r = 0·888, P < 0001). This correlation was found irrespective of different types of hypertension and treatment schedules. 3. During volume depletion, PRA was stimulated and renin dependency of the blood pressure increased. Propranolol therapy suppressed PRA during normovolaemia as well as during volume depletion, and this was accompanied by a decrease of the renin dependency. 4. No indication was found that a given PRA is of special importance for blood pressure elevation in different patients. 5. Suppression of PRA by propranolol is one of the anti-hypertensive mechanisms of this drug.

scholarly journals Pharmacodynamic Effects of an Angiotensin II Receptor-Antagonist in Phase I—Comparison between Healthy Subjects and Patients with Hypertension

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Georg Wensing ◽  
Klaus Ochmann ◽  
Michael Boettcher ◽  
Anja Schäfer ◽  
Jochen Kuhlmann
Keyword(s):  
Angiotensin Ii ◽  
Phase I ◽  
Healthy Volunteers ◽  
Receptor Antagonist ◽  
Healthy Subjects ◽  
Antihypertensive Agents ◽  
Plasma Renin ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Antagonist ◽  
Hypertensive Patients

Biomarkers are increasingly used to provide decision making data early in phase I by showing Proof of Mechanism or Proof of Concept (PoM/PoC). For antihypertensive agents, the administration of multiple doses (md) to hypertensive patients is assumed to be necessary for an early go/no-go decision. We compared the effects of an Angiotensin II receptor antagonist (ARA) on Plasma Renin and blood pressure (BP) following an oral single dose (sd) and once daily md for seven days to healthy volunteers and patients with essential hypertension (diastolic BP 95 mmHg to 114 mmHg; systolic BP 130 mmHg to 200 mmHg). Methods: 5–12 healthy male subjects/dose received 10 mg to 300 mg ARA sd and 50 to 300 mg md for 7 days; patients (9–10/dose) received 20 mg–400 mg ARA for 7 days. The studies were designed as randomized, single blind, placebo-controlled, group comparison or crossover dose-escalation studies. Plasma Renin and BP were monitored up to 24 hours after dosing. Results: Plasma Renin showed a high interindividual variability in both healthy volunteers and patients. Healthy subjects showed a dose- and time-related increase in plasma Renin after sd from 40 mg to 300 mg and md of 50 mg to 300 mg (p < 0.05 for doses of 200 mg and 300 mg). In patients, increases in plasma Renin occurred at 8 hours and beyond starting at sd of 100 mg and md of 50 mg (p < 0.05 for the dose of 400 mg). While healthy volunteers showed no relevant decrease in BP, in hypertensive patients a reduction in BP in doses of 100 mg to 400 mg occurred (p < 0.05); effects were more pronounced after md compared to sd. Conclusion: Early PoM for an antihypertensive agent can be shown by use of laboratory biomarkers following sd to healthy subjects. PoC can be achieved after sd in hypertensive patients. Administration of sd to healthy volunteers is sufficient for an early go/no-decision.

Effects of Felodipine and Metoprolol on Blood Pressure, Plasma Renin, Angiotensin II, Aldosterone and Catecholamines in Hypertensive Patients

Drugs ◽  
1987 ◽  
Vol 34 (Supplement 3) ◽  
pp. 170-175 ◽  
Author(s):  
P. Lijnen ◽  
R. Fagard ◽  
J. Staessen ◽  
E. Moerman ◽  
A. De Schaepdryver ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin ◽  
Hypertensive Patients ◽  
Renin Angiotensin ◽  
Pressure Plasma

Effect of Sotalol on Haemodynamics and Renin—Angiotensin—Aldosterone System in Hypertensive Patients

1976 ◽  
Vol 51 (1) ◽  
pp. 9-17 ◽  
Author(s):  
A. Verniory ◽  
M. Staroukine ◽  
F. Delwiche ◽  
M. Telerman
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Cardiac Index ◽  
Total Peripheral Resistance ◽  
Excretion Rate ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Hypertensive Patients ◽  
Receptor Blocking ◽  
Plasma Angiotensin

1. Twenty-three hypertensive patients were treated by sotalol, a pure beta-adrenergic receptor blocking agent. The drug produced a significant decrease of blood pressure in nineteen patients. 2. On average, cardiac index decreased but not significantly; heart rate decreased and stroke index increased significantly. Total peripheral resistance varied in both directions. 3. Sotalol determined a fall in plasma renin concentration (only significant in the high-renin group), a fall in plasma angiotensin II concentration and in urinary excretion rate of aldosterone accompanied by a rise in plasma potassium concentration. 4. The fall of blood pressure was not correlated with the decreases of renin and angiotensin II concentrations or excretion rate of aldosterone. However, in the placebo period plasma angiotensin II concentration was significantly correlated with total peripheral resistance; during sotalol treatment the variations of these two parameters seemed also to be correlated. 5. There was a poor correlation between decreases of cardiac output and of blood pressure; it was impossible to foresee the magnitude of the lowering of the blood pressure from the initial cardiac index. 6. The association of a diuretic with sotalol enhanced the hypotensive effect of the beta-receptor blocking drug, without significant increase of plasma renin and angiotensin II concentrations.

Humoral Effects of the Oral Converting-Enzyme Inhibitor Sq 14 225 in Hypertensive Patients in Supine and Tilted Position

1979 ◽  
Vol 57 (s5) ◽  
pp. 149s-152s ◽  
Author(s):  
A. Morganti ◽  
T. G. Pickering ◽  
J. Lopez-Ovejero ◽  
J. H. Laragh
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Nervous System ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Hypertensive Patients ◽  
Sympathetic Nervous

1. To evaluate the effects of converting-enzyme inhibition on the sympathetic nervous system, on renin and on the other known regulators of aldosterone secretion, we measured blood pressure, heart rate, plasma noradrenaline, adrenaline, renin activity, aldosterone, cortisol and serum potassium in 15 sodium-repleted hypertensive patients in supine position and during 30 min of 65° head-up tilt before and during treatment with SQ 14 225. 2. SQ 14 225 produced significant decreases in supine blood pressure and plasma aldosterone and significant increments in plasma renin activity and potassium; in contrast, heart rate, noradrenaline, adrenaline and cortisol were unchanged. 3. While in control tilt studies blood pressure was always maintained, during treatment three of 15 patients had vasovagal syncopes. In the remaining 12 blood pressure was maintained during tilt on SQ 14 225; however, while the tilt-induced responses in heart rate and adrenaline were as in control studies, the 30 min increments in noradrenaline were significantly higher. 4. Both before and during treatment the responses of plasma renin activity and aldosterone to tilt were parallel, and correlated with each other, and cortisol and potassium changed only slightly. 5. It is concluded that the SQ 14 225-induced fall in blood pressure occurs without a concomitant rise in sympathetic nervous activity; thus the increase in supine plasma renin activity, being a reflection of the interruption of the angiotensin feedback mechanism on renin release, indicates an effective suppression of angiotensin II formation. 6. During SQ 14 225 the persistence of aldosterone response to tilt and its relationship with renin activity suggest that the enzymatic blockade is over-ridden; however, in the presence of a reduced formation of angiotensin II a more pronounced response of the sympathetic nervous system is required to defend blood pressure against postural changes.

Effect of Early Normotension with Olmesartan on Rho-kinase Activity in Hypertensive Patients

2019 ◽  
Vol 18 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Claudio Cantin ◽  
Jorge E. Jalil ◽  
Juan F. Bulnes ◽  
Ulises Novoa ◽  
Paul MacNab ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Kinase Activity ◽  
Clinical Evidence ◽  
Mononuclear Cells ◽  
Treatment Initiation ◽  
Rho Kinase ◽  
Angiotensin Ii Receptor ◽  
Peripheral Blood Mononuclear ◽  
Hypertensive Patients ◽  
Rock Activity

Background: Angiotensin II is a potent activator of the Rho-kinase (ROCK) pathway, through which it exerts some of its adverse vasoconstrictor effects. Clinical evidence on the effects of blocking the angiotensin II receptor 1 on ROCK activity in hypertensive patients is scarce. Objective: To demonstrate that ROCK activity in peripheral blood mononuclear cells (PMBCs) in patients with essential hypertension is reduced earlier than previously observed, along with blood pressure (BP) lowering on treatment with olmesartan. Methods: Prospective pilot open study; 17 hypertensive patients were treated with progressive olmesartan doses starting with 20 mg qd. BP was measured at 3, 6 and 9 weeks after treatment initiation. If treatment failed to normalize BP after 3 weeks, olmesartan dose was increased to 40 mg qd, and if still hypertensive after 6 weeks, 12.5 mg of hydrochlorothiazide qd was added. ROCK activity was measured at baseline and 9 weeks after treatment as myosin phosphatase target subunit 1 phosphorylation (MYPT1-p/T ratio) in PBMC. Results: Mean baseline BP was 162 ± 4.9/101 ± 2.4 mmHg. After 9 weeks of treatment, both systolic and diastolic BP were reduced by 41 and 22 mmHg, respectively (p<0.05). Mean pretreatment MYPT1- p/T ratio in PMBCs was significantly reduced by 80% after 9 weeks with olmesartan (p<0.01). Conclusion: Normotension achieved after 9 weeks in 82% of the patients treated with olmesartan was associated with a significant reduction of ROCK activity in PBMC.

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