scholarly journals Arterial Hypertension: Individual Therapeutic Approaches—From DNA Sequencing to Gender Differentiation and New Therapeutic Targets

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 856
Author(s):  
Constantin-Tudor Luca ◽  
Simina Crisan ◽  
Dragos Cozma ◽  
Alina Negru ◽  
Mihai-Andrei Lazar ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Dna Sequencing ◽  
Antihypertensive Treatment ◽  
Nervous Activity ◽  
Renin Angiotensin System ◽  
Uncontrolled Hypertension ◽  
Sympathetic Nervous Activity ◽  
Lower Systolic Blood Pressure ◽  
Female Patients ◽  
Treatment Individualization

The aim of this paper is to provide an accurate overview regarding the current recommended approach for antihypertensive treatment. The importance of DNA sequencing in understanding the complex implication of genetics in hypertension could represent an important step in understanding antihypertensive treatment as well as in developing new medical strategies. Despite a pool of data from studies regarding cardiovascular risk factors emphasizing a worse prognosis for female patients rather than male patients, there are also results indicating that women are more likely to be predisposed to the use of antihypertensive medication and less likely to develop uncontrolled hypertension. Moreover, lower systolic blood pressure values are associated with increased cardiovascular risk in women compared to men. The prevalence, awareness and, most importantly, treatment of hypertension is variable in male and female patients, since the mechanisms responsible for this pathology may be different and closely related to gender factors such as the renin–angiotensin system, sympathetic nervous activity, endothelin-1, sex hormones, aldosterone, and the immune system. Thus, gender-related antihypertensive treatment individualization may be a valuable tool in improving female patients’ prognosis.

Splanchnic vasoconstriction in heat-stressed men: role of renin-angiotensin system

1982 ◽  
Vol 52 (6) ◽  
pp. 1438-1443 ◽  
Author(s):  
P. Escourrou ◽  
P. R. Freund ◽  
L. B. Rowell ◽  
D. G. Johnson
Keyword(s):  
Heat Stress ◽  
Arterial Pressure ◽  
Nervous Activity ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Sympathetic Nervous Activity ◽  
Plasma Norepinephrine ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Norepinephrine Concentration

We conducted a two-part study to determine whether the renin-angiotensin system contributes to the rise in splanchnic vascular resistance (SVR) during heat stress (rectal temperature was raised 1 degree C). In experiment 1 (control) seven men on a normal salt diet were directly heated (water-perfused suits) for 40–50 min. Arterial pressure (85 Torr) was unchanged; plasma renin activity (PRA) rose from 102 to 239 ng angiotensin I.100 ml-1.3 h-1; and SVR increased 73% (from 63 to 109 units). Experiment 2 was a repetition of experiment 1 on the same subjects, except that propranolol (10 mg iv) was given at the onset of heating to block renin release. Propranolol attenuated the rise in heart rate and reduced mean arterial pressure from 82 to 72 Torr; it blocked the rise in PRA with heating in two subjects, reduced it in three, but increased it in two. Although changes in SVR paralleled those in PRA in three subjects, SVR still rose 60% (from 58 to 99 units) after PRA rise was blocked. In both experiments, plasma norepinephrine concentration rose indicating increased sympathetic nervous activity. During mild heat stress, increased PRA is not a major factor in the increase of SVR.

scholarly journals Determining Risk Factors for Triple Whammy Acute Kidney Injury

2021 ◽  
Author(s):  
Jessica Leete ◽  
Carolyn Wang ◽  
Francisco Lopez-Hernandez ◽  
Anita Layton
Keyword(s):  
Acute Kidney Injury ◽  
Computational Models ◽  
Enzyme Inhibitor ◽  
Nervous Activity ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Sympathetic Nervous Activity ◽  
Physiological Factors ◽  
Concurrent Use ◽  
Individual Variations

Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as "triple whammy". Diuretics and RAS inhibitors, such as an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common. The goals of this study are to better understand the mechanisms underlying the development of triple whammy AKI and to identify physiological factors that may increase an individual's susceptibility. To accomplish these goals, we utilize computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that individual variations in water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI.

Fifty years of research on the brain renin–angiotensin system: what have we learned?

2021 ◽  
Vol 135 (14) ◽  
pp. 1727-1731
Author(s):  
Edwyn O. Cruz-López ◽  
Estrellita Uijl ◽  
A.H. Jan Danser
Keyword(s):  
Brain Tissue ◽  
Nervous Activity ◽  
Renin Angiotensin System ◽  
Sympathetic Nervous Activity ◽  
Ang Ii ◽  
Angiotensin System ◽  
Future Studies ◽  
Renin Angiotensin ◽  
Aminopeptidase A ◽  
The Brain

Abstract Although the existence of a brain renin–angiotensin system (RAS) had been proposed five decades ago, we still struggle to understand how it functions. The main reason for this is the virtual lack of renin at brain tissue sites. Moreover, although renin’s substrate, angiotensinogen, appears to be synthesized locally in the brain, brain angiotensin (Ang) II disappeared after selective silencing of hepatic angiotensinogen. This implies that brain Ang generation depends on hepatic angiotensinogen after all. Rodrigues et al. (Clin Sci (Lond) (2021) 135:1353–1367) generated a transgenic mouse model overexpressing full-length rat angiotensinogen in astrocytes, and observed massively elevated brain Ang II levels, increased sympathetic nervous activity and vasopressin, and up-regulated erythropoiesis. Yet, blood pressure and kidney function remained unaltered, and surprisingly no other Ang metabolites occurred in the brain. Circulating renin was suppressed. This commentary critically discusses these findings, concluding that apparently in the brain, overexpressed angiotensinogen can be cleaved by an unidentified non-renin enzyme, yielding Ang II directly, which then binds to Ang receptors, allowing no metabolism by angiotensinases like ACE2 and aminopeptidase A. Future studies should now unravel the identity of this non-renin enzyme, and determine whether it also contributes to Ang II generation at brain tissue sites in wildtype animals. Such studies should also re-evaluate the concept that Ang-(1-7) and Ang III, generated by ACE2 and aminopeptidase A, respectively, have important functions in the brain.

Sympathetic nervous activity in carriers of MC4R mutations

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
D Heutling ◽  
F Sayk ◽  
C Dodt ◽  
HL Fehm ◽  
A Hinney ◽  
...  
Keyword(s):  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous

Device therapy of resistant hypertension

2013 ◽  
Vol 154 (6) ◽  
pp. 203-208 ◽  
Author(s):  
Gábor Simonyi ◽  
J. Róbert Bedros ◽  
Mihály Medvegy
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Resistant Hypertension ◽  
Carotid Sinus ◽  
Maximum Tolerated Dose ◽  
Reduce Blood Pressure ◽  
Nerve Fibers ◽  
Uncontrolled Hypertension ◽  
Sympathetic Nerve Fibers ◽  
Treatment Of Hypertension

It is well known that hypertension is an independent cardiovascular risk factor. Treatment of hypertension frequently includes administration of three or more drugs. Resistant hypertension is defined when blood pressure remains above target value despite full doses (the patient’s maximum tolerated dose) of antihypertensive medication consisting of at least three different classes of drugs including a diuretic. Pharmacological treatment of hypertension is often unsuccessful despite the increasing number of drug combinations. Uncontrolled hypertension, however, increases the cardiovascular risk. Device treatment of resistant hypertension is currently testing two major fields. One of them the stimulation of baroreceptors in the carotid sinus and the other is radiofrequency ablation of sympathetic nerve fibers around renal arteries to reduce blood pressure in drug resistant hypertension. Orv. Hetil., 2013, 154, 203–208.

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