Blood Pressure Regulation

Using major components of the Guyton model of circulation (Guyton 1972), along with the additions of renal sympathetic nervous activity (RSNA, Karaaslaan et al. 2005), and the renin angiotensin system (RAS, Hallow et al. 2013) we propose a model of blood pressure regulation fitted separately for male and female humans (Leete and Layton 2018). Sex differences include RSNA, the RAS, and aldosterone levels.

Using this model, we investigated differences in anti-hypertensive therapy efficacy for angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB).

Concurrent use of diuretics, ACEI/ARB, and nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of acute kidney injury (AKI). AKI resulting from use of all three drugs is referred to as “triple whammy” AKI. Diuretics and ACEI/ARB are often prescribed in tandem for the treatment of hypertension while some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common.

We investigate mechanisms behind the increased risk of AKI and identify potential risk factors, including individual variations in regulatory mechanisms, such as tubuloglomerular feedback, the myogenic effect, and renal sympathetic nervous activity as well as physiological variables that induce hypotension, including low water intake. Understanding how each of these drugs affect renal autoregulation individually and in combination can help medical providers avoid prescribing dangerous combination in at risk individuals and administer them with confidence to low risk patients, especially to those who may benefit from pain killers for acute or chronic pain relief.

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