Intensive blood pressure control in chronically hypertensive mice

Abstract

It is estimated that 1.13 billion people worldwide have hypertension and this is expected to increase to 1.56 billion by 2025 due to population growth, ageing and lifestyle factors such as diet, obesity, and lack of exercise. Direct and indirect costs related to hypertension globally are estimated to cost in excess of $3 trillion (USD). In pregnancy, the definition of hypertension is generally defined as repeated blood pressure measurements above 140/90mmHg. Preeclampsia (PE) is the most severe of the hypertensive disorders of pregnancy and women with chronic hypertension have at least five times the risk of preeclampsia compared to women with normal blood pressure. Even when uncomplicated by preeclampsia, chronically hypertensive women are at double the risk of small for gestational age neonates. Once a woman becomes pregnant, guidelines for when to commence antihypertensive treatment lack consensus and there is a lack of data regarding treatment in early pregnancy of women with chronic hypertension. Using an animal model of chronically hypertensive mice that develop a preeclampsia-like illness during pregnancy, this study aims to eventually determine whether 'tight' blood pressure control (diastolic blood pressure of 60mmHg) or 'moderate' blood pressure control (diastolic blood pressure of 80mmHg) during early pregnancy affects placentation and fetal weight. This study aimed to complete preliminary work to 1. Compare indirect and direct methods of blood pressure measurement in C57BL/6 and BPH/2J mice (tail cuff vs telemetry) 2. Identify a drug, dose and/or combination that will reduce the average resting diastolic blood pressure of C57BL/6 and BPH/2J mice to 'tight' (60) and 'moderate' (80) mmHg targets. We established that telemetry is the preferred method of obtaining blood pressure data and that tail cuff measurements are unlikely to be suitable for the detail required for this study. No drug was required to achieve the 'moderate' diastolic blood pressure target (80mmHg) in the normotensive strain (C57BL/6JAusb) and 20mg/kg labetalol plus 4-10mg/kg hydralazine successfully achieved this target in the hypertensive strain (BPH/2J). Further investigation is required to identify a drug or combination of drugs that reliably reduces the average resting diastolic blood pressure in both normotensive and hypertensive strains of mice to the 'tight' target (60mmHg).

Date of Award	2020
Original language	English