Renin Profiling to Select Anti hypertensive Baseline Drugs: Renin Inhibitors for High-Benin and Calcium Entry Blockers for Low-Benin Patients

doi:10.1016/S0002-9343(84)80056-X

The American Journal of Medicine

Volume 77, Issue 2, Part 1, 20 August 1984, Pages 36-42

https://doi.org/10.1016/S0002-9343(84)80056-X Get rights and content

Renin profiling stimulated research into the pathophysiology of essential hypertension and influenced the development of antihypertensive treatment strategies. Patients with a high renin value and usually younger age respond better to drugs that interfere with the renin-angiotensin system, that is, beta blockers or converting enzyme inhibitors. Patients with a low renin value and often older age respond better to calcium entry blockers or diuretics. Patients with normal renin levels exhibit mixed but, on average, equal responses to these types of drugs. A pathophysiology-oriented antihypertensive treatment strategy is proposed in which beta blockers or converting enzyme inhibitors are used as one and calcium entry blockers-in the place of diuretics when possible-as the other baseline drug, and this approach may provide a cardiac-protective effect.

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Redefining beta-blocker use in hypertension: selecting the right beta-blocker and the right patient
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Citation Excerpt :
If this is the main mechanism of BP lowering, then one would expect that beta-blockers would be more effective in patients with normal or high renin levels than in patients with low-renin levels. This has been consistently demonstrated.77–80 One would also expect a strong positive correlation between response to beta-blockers and response to ACE inhibitors, if both target the same mechanism.
Randomized controlled trials have concluded that the cardiovascular outcome of first-step treatment of hypertension with traditional vasoconstricting beta-blockers is inferior to treatment with other antihypertensive drug classes. Beta-blocker use is also associated with undesirable side effects. Consequently, some recent guidelines consider beta-blockers an inferior option for first-step treatment of hypertension. Despite this, beta-blockers are still widely prescribed, and likely overused, in the management of hypertension. It is the contention of this perspective that beta-blockers do have an important role in treating hypertension, but their use needs to be much better targeted, by better identification of both the right patient and the right beta-blocker. Identifying the right patient involves consideration of underlying mechanisms of hypertension. In the absence of comorbidities for which a beta-blocker is indicated, beta-blockers would not seem to be the preferred treatment for patients with either sodium/volume-mediated hypertension, for which they are usually ineffective, or for those with renin-angiotensin system–mediated hypertension, for which angiotensin-converting enzyme inhibitors and angiotensin receptor blockers provide equal antihypertensive efficacy with evidence of better outcome and fewer adverse effects. Beta-blockers would instead appear to be best suited for patients with sympathetically driven, that is, neurogenic, hypertension, whether as a first-step drug, such as in patients with hypertension in the acute post-stroke period, in so-called “hyperkinetic” patients, and in patients with labile hypertension, or as an add-on drug in patients with resistant hypertension. In choosing among the beta-blockers, combined alpha/beta-blockade offers advantages over beta-blocker monotherapy and merits greater clinical and research attention. Finally, unreliable bioavailability greatly interferes with the effectiveness of lipophilic, but not nonlipophilic, beta-blockers. Clinical effectiveness could be improved with greater focus on the beta-blockers with the more favorable pharmacokinetics.
Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: How useful, how feasible?
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Citation Excerpt :
Thus, the majority of patients with primary hypertension do not have low renin levels, possibly following the higher perfusion pressure at the juxtaglomerular cells which suppresses renin release. Nonetheless, it has been argued that a normal renin level in the face of hypertension, which is supposed to suppress renin secretion, may be inappropriate [43]. Renin profiling has been identified as a valuable tool for therapeutic optimization in hypertension since late '70s [44].
Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of biomarkers of the RAAS activation, as a guide to tailor individual therapy in the current practice, and their implementation as a rule-in marker for future trials on novel drugs in the heart failure setting.
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2015, Endocrinology: Adult and Pediatric
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Citation Excerpt :
RAAS is involved in certain forms of secondary hypertension, including renin-secreting neoplasms, renovascular hypertension (eg, renal artery stenosis), malignant hypertension, pheochromocytoma, and primary hyperaldosteronism. In patients with primary (essential) hypertension, the plasma renin activity (PRA) can be high, normal, or low.19 “Low-renin” hypertension is more commonly seen in the elderly, diabetic patients, and those with chronic renal parenchymal disease.
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2010, Endocrinology: Adult and Pediatric, Sixth Edition
Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney
2003, American Journal of Medicine
Citation Excerpt :
They also lead to fewer cardiovascular events among high-risk patients, such as those with vascular disease (20). Some patients with high plasma renin activities, such as those with renal artery stenosis, respond well to treatment with ACE inhibitors, as compared with African Americans and the elderly, who are more likely to have essential hypertension and low renin levels (21). Angiotensin-converting enzyme inhibitors are most effective in lowering blood pressure in patients who are on sodium-restricted diets or who are also taking diuretics (22).
Many clinicians are uncomfortable about using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (AT₁-blockers) to treat patients with renal disease because of concerns about increasing serum creatinine levels. However, the benefits of these medications, particularly their efficacy in slowing the progression of renal disease, outweigh such concerns. ACE inhibitors are effective in patients with type 1 diabetes and renal disease, as well as in those with nondiabetic renal disease and proteinuria >0.5 g/d. AT₁-blockers slow the progression of diabetic nephropathy in patients with type 2 diabetes. Although these classes of medications should not be used in patients with severe renal insufficiency (e.g., glomerular filtration rate <20 mL/min), they may be beneficial in patients with mild-to-moderate renal insufficiency. Nonetheless, caution should be exercised in those with a glomerular filtration rate <30 mL/min, and serum creatinine and potassium levels should be checked approximately 1 week after starting treatment. There is also evidence suggesting that these medications lead to greater reductions in blood pressure and proteinuria when used in combination than when alone. The purpose of this paper is to review the mechanisms of action of these two classes of medication, as well as the experimental and clinical evidence that they slow the progression of renal disease.

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^b: From the Division of Cardiology, University Hospital, Basel, Switzerland.

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Renin Profiling to Select Anti hypertensive Baseline Drugs: Renin Inhibitors for High-Benin and Calcium Entry Blockers for Low-Benin Patients

Am J Med

Am J Cardiol

Am J Med

Am J Cardiol

Am J Med

A pharmacological tool to identify pathogenetic mechanisms in essential hypertension. Am J Cardiol

Am J Med

Am J Med

Prog Cardiovasc Dis

Lancet

Am J Cardiol

Essential hypertension:renin and aldosterone, heart attack and stroke

N Engl J Med

Propranolol inhibition of renin secretion:a specific approach to diagnosis and treatment of renin-dependent hypertensive diseases

N Engl J Med

Hypertension in man:exposure of the renin and sodium components using angiotensin II blockade

Circ Res

An angiotensin-converting enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients

N Engl J Med

Renin subgroups in essential hypertension

Circ Res

Decreased betaadrenoceptor responsiveness as related to age, blood pressure and plasma catecholamines in patients with essential hypertension

Hypertension

Changing role of beta and alpha-adrenoceptor-mediated cardiovascular responses in the transition from a high cardiac output into a high periph eral resistance phase in essential hypertension

Enhanced alpha adrenoceptor-mediated vasoconstriction in essential hypertension

Hypertension

Factors influencing the hypotension effect of calcium antagonists

Hypertension

Antihypertehsive action of betablockers

How intrinsic sympathomimetic activity modulates the haemodynamic responses to beta-adrenoceptor antagonists. A clue to the nature of their anti hypertensive mechanism

Br J Clin Pharmacol

Does the reninangiotensin system maintain blood pressure in both hypertensive and normotensive subjects? A comparison of propranolol, saralasin and captopril

Clin Sci

Role of alpha-adrenoceptor-mediated vasoconstriction for ahtihypertensive beta blockade

J Cardiovasc Pharmacol