Regulation of blood pressure by the type 1A angiotensin II receptor gene.

The renin-angiotensin system plays a critical role in sodium and fluid homeostasis. Genetic or acquired alterations in the expression of components of this system are strongly implicated in the pathogenesis of hypertension. To specifically examine the physiological and genetic functions of the type 1A receptor for angiotensin II, we have disrupted the mouse gene encoding this receptor in embryonic stem cells by gene targeting. Agtr1A(-/-) mice were born in expected numbers, and the histomorphology of their kidneys, heart, and vasculature was normal. AT1 receptor-specific angiotensin II binding was not detected in the kidneys of homozygous Agtr1A(-/-) mutant animals, and Agtr1A(+/-) heterozygotes exhibited a reduction in renal AT1 receptor-specific binding to approximately 50% of wild-type [Agtr1A(+/+)] levels. Pressor responses to infused angiotensin II were virtually absent in Agtr1A(-/-) mice and were qualitatively altered in Agtr1A(+/-) heterozygotes. Compared with wild-type controls, systolic blood pressure measured by tail cuff sphygmomanometer was reduced by 12 mmHg (1 mmHg = 133 Pa) in Agtr1A(+/-) mice and by 24 mmHg in Agtr1A(-/-) mice. Similar differences in blood pressure between the groups were seen when intraarterial pressures were measured by carotid cannulation. These studies demonstrate that type 1A angiotensin II receptor function is required for vascular and hemodynamic responses to angiotensin II and that altered expression of the Agtr1A gene has marked effects on blood pressures.

Predictive regression equations and clinical uses of peripheral pulse timing characteristics in children

Studies have shown that increased arterial stiffening can be an indication of cardiovascular diseases like hypertension. In clinical practice, this can be detected by measuring the blood pressure (BP) using a sphygmomanometer but it cannot be used for prolonged monitoring. It has been established that pulse wave velocity (PWV) is a direct measure of arterial stiffening but its usefulness is hampered by the absence of non-invasive techniques to estimate it. Pulse transit time (PTT) is a simple and non-invasive method derived from PWV. However, limited knowledge of PTT in children is found in the present literature. The aims of this study are to identify independent variables that confound PTT measure and describe PTT regression equations for healthy children. Therefore, PTT reference values are formulated for future pathological studies. Fifty-five Caucasian children (39 male) aged 8.4 +/- 2.3 yr (range 5-12 yr) were recruited. Predictive equations for PTT were obtained by multiple regressions with age, vascular path length, BP indexes and heart rate. These derived equations were compared in their PWV equivalent against two previously reported equations and significant agreement was obtained (p < 0.05). Findings herein also suggested that PTT can be useful as a continuous surrogate BP monitor in children.

Use of regression equation of peripheral pulse timing characteristics to predict hypertension in children

Studies have shown that an increase in arterial stiffening can indicate the presence of cardiovascular diseases like hypertension. Current gold standard in clinical practice is by measuring the blood pressure of patients using a mercury sphygmomanometer. However, the nature of this technique is not suitable for prolonged monitoring. It has been established that pulse wave velocity is a direct measure of arterial stiffening. However, its usefulness is hampered by the absence of techniques to estimate it non-invasively. Pulse transit time (PTT) is a simple and non-intrusive method derived from pulse wave velocity. It has shown its capability in childhood respiratory sleep studies. Recently, regression equations that can predict PTT values for healthy Caucasian children were formulated. However, its usefulness to identify hypertensive children based on mean PTT values has not been investigated. This was a continual study where 3 more Caucasian male children with known clinical hypertension were recruited. Results indicated that the PTT predictive equations are able to identify hypertensive children from their normal counterparts in a significant manner (p < 0.05). Hence, PTT can be a useful diagnostic tool in identifying hypertension in children and shows potential to be a non-invasive continual monitor for arterial stiffening.

The clinical assessment of systemic hypertension in optometric practice

This thesis sets out to examine in detail the condition of systemic hypertension (high Blood Pressure) in relation to optometric practice in the United Kingdom. Systemic hypertension, which is asymptomatic in the early stages, is diagnosed from the Blood Pressure (BP) measurement recorded by a sphygmomanometer and/or from the complications that have developed in target organs. Optometric practice based surveys revealed that diagnosed systemic hypertension was the most prevalent cardiovascular medical condition (20.5%). Measurement of BP of patients in this sample revealed that if an optometrist included sphygmomanometry into the sight examination then at least one patient each day would be referred for suspect systemic hypertension. Optometric opinion felt that the measurement of BP in optometric practice would advance the profession, being appreciated by both patients and General Practitioners (GPs), but was felt to be an unnecessary routine procedure. The present sight examination for the systemic hypertensive is similar to that of the normotensive patient, but may involve an altered fundus examination and a visual field test. The GPs were in favour of optometric BP measurement and a future role in the share care management of the systemic hypertensive. The application of a new pictorial grading scale for the grading of vascular changes associated with pre-malignant systemic hypertension was found to be both accurate and reliable. Clinical trial of the grading scale in optometric practice found positive correlations between BP and increasing severity of the retinal vascular features. The subtle pre-malignant vascular changes require reliable accurate detection and analysis to assist in the management of the systemic hypertensive patient. Vessel width was shown to decrease with increasing age. Image analysis of the A/V ratio, arteriolar tortuosity and focal calibre changes revealed a positive correlation to the patient's BP (p<0.001). The retinal vasculature is relatively stable longitudinally with only minor changes in response to early disease states. Age and elevated BP increased a patient's risk of developing systemic medical conditions over a two-year period. The application of the pictorial grading scale to optometric practice and training the optometrist in the use of sphygmomanometry would improve the management of the systemic hypertensive patient in optometric practice. Future advances in image analysis hold substantial benefits for the detection and monitoring of subtle vascular changes associated with systemic hypertension.