Calcium Channel Inhibitors for Identification of Mechanisms and Treatment of Hypertension

Fr, Bühler; Ul, Hulthén; Bolli, Peter

doi:10.1097/00005344-198200433-00001

Cited by 6 publications

(2 citation statements)

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“…Understanding of these secondary forms, together with mechanisms discovered in primary hypertension, such as renal salt and water metabolism, the renin-angiotensin aldosterone system, the functioning of pre- and postsynaptic receptors of the adrenergic nervous system, and mechanisms of calcium entry into vascular smooth muscle cells, led to antihypertensive drug development based on molecular targets identified by such research. Early on, using the understanding of these mechanisms in primary hypertension, attempts were made to personalize treatment at the individual patient level [ 2 , 3 •]. However, such treatment approaches had little chance to succeed given the powerful financial interests of pharmaceutical manufacturers who advocated every newly approved drug to reduce blood pressure in every hypertensive patient.…”

Section: Current Antihypertensive Drug Treatment Was Built On a Largementioning

confidence: 99%

AI (Artificial Intelligence) and Hypertension Research

Mueller

2020

Curr Hypertens Rep

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Purpose of Review This review a highlights that to use artificial intelligence (AI) tools effectively for hypertension research, a new foundation to further understand the biology of hypertension needs to occur by leveraging genome and RNA sequencing technology and derived tools on a broad scale in hypertension. Recent Findings For the last few years, progress in research and management of essential hypertension has been stagnating while at the same time, the sequencing of the human genome has been generating many new research tools and opportunities to investigate the biology of hypertension. Cancer research has applied modern tools derived from DNA and RNA sequencing on a large scale, enabling the improved understanding of cancer biology and leading to many clinical applications. Compared with cancer, studies in hypertension, using whole genome, exome, or RNA sequencing tools, total less than 2% of the number cancer studies. While true, sequencing the genome of cancer tissue has provided cancer research an advantage, DNA and RNA sequencing derived tools can also be used in hypertension to generate new understanding how complex protein network, in non-cancer tissue, adapts and learns to be effective when for example, somatic mutations or environmental inputs change the gene expression profiles at different network nodes. The amount of data and differences in clinical condition classification at the individual sample level might be of such magnitude to overwhelm and stretch comprehension. Here is the opportunity to use AI tools for the analysis of data streams derived from DNA and RNA sequencing tools combined with clinical data to generate new hypotheses leading to the discovery of mechanisms and potential target molecules from which drugs or treatments can be developed and tested. Summary Basic and clinical research taking advantage of new gene sequencing-based tools, to uncover mechanisms how complex protein networks regulate blood pressure in health and disease, will be critical to lift hypertension research and management from its stagnation. The use of AI analytic tools will help leverage such insights. However, applying AI tools to vast amounts of data that certainly exist in hypertension, without taking advantage of new gene sequencing-based research tools, will generate questionable results and will miss many new potential molecular targets and possibly treatments. Without such approaches, the vision of precision medicine for hypertension will be hard to accomplish and most likely not occur in the near future. Keywords Artificial intelligence. Deep machine learning algorithms. Whole genome and RNA sequencing. Hypertension treatment. Gene and protein networks. Target molecules. Cancer and hypertension research publications

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Section: Current Antihypertensive Drug Treatment Was Built On a Largementioning

confidence: 99%

AI (Artificial Intelligence) and Hypertension Research

Mueller

2020

Curr Hypertens Rep

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“…The dihydropyridine calcium entry blockers, such as nifedipine, are antihypertensive agents that are effective in lowering blood pressure in hypertensive patrients, either when given alone [1][2][3][4] or in combination with other drugs [5][6][7].…”

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Calcium-channel blockers and sodium intake: A controlled study in patients with essential hypertension

Galletti

Strazzullo

Cappuccio

et al. 1989

Cardiovasc Drug Ther

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Thirteen patients with mild to moderate essential hypertension and whose average supine blood pressure with no treatment was 165/104 mmHg were studied as inpatients for 3 consecutive one-week periods on different sodium intakes. On the last day of each dietary period, they received a single, 20-mg nitrendipine tablet and blood pressure was monitored every 10 minutes for 2 hours after drug administration. Nitrendipine significantly lowered blood pressure independently of the level of sodium intake, and the maximum blood-pressure lowering effect was achieved approximately 1 hour after the dose. The blood-pressure lowering effect of nitrendipine was greater on high sodium intake as compared to low sodium intake (p less than 0.02), and it was also greater with higher initial blood pressures. However, the sodium-related effect on blood pressure was, at least in part, independent of the pretreatment blood pressure. These results suggest that calcium antagonists, such as nitrendipine, are effective in reducing blood pressure in patients with essential hypertension and could be drugs of choice in those who are unable to restrict their salt intake.

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Zunahme des Leberblutflusses unter Nifedipin

1986

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The hepatic hemodynamic effect of 20 mg sublingual nifedipine was evaluated in 15 patients (13 men, 2 women) during heart catheterization. The liver blood flow was measured 10 min after administration of nifedipine by continuous thermodilution (Baim coronary sinus flow analyzer). Nifedipine was associated with a decrease in systolic blood pressure (from 156 +/- 14 to 138 +/-13 mmHg), an increase in heart rate (from 73 +/- 13 to 81 +/- 8.6 beats/min), and increase in cardiac output (from 6.0 +/- 1.6 to 6.5 +/- 1.3 l/min). In 2/15 patients no significant change was derived. The liver blood flow increased in 13/15 patients from 218 +/- 171.7 to 336.7 +/- 247.7 ml/min (22%-194%, P less than 0.01). The study demonstrates that the vasodilation of nifedipine involves the hepatic circulation. If the hepatic clearance of drugs is high and flow dependent, nifedipine-induced increase of hepatic blood flow may impair drug clearance.

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Calcium Channel Inhibitors for Identification of Mechanisms and Treatment of Hypertension

Cited by 6 publications

References 0 publications

AI (Artificial Intelligence) and Hypertension Research

AI (Artificial Intelligence) and Hypertension Research

Calcium-channel blockers and sodium intake: A controlled study in patients with essential hypertension

Zunahme des Leberblutflusses unter Nifedipin

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