High blood pressure: hunting the genes.

High blood pressure is a disease of unknown cause. Family history of the disease indicates higher risk, but it is not known which genes are involved or how they interact with environmental influences to produce the disorder. Molecular biology offers an approach to problems that have not so far been solved by classical physiology or biochemistry. By analysing polymorphic variation in chromosome markers such as minisatellite sequences, or by restriction fragment polymorphism analysis of candidate genes, attempts are being made to link genetic variations with hypertension. In genetically hypertensive rats, hypertension is associated with a polymorphism of the renin gene and with other loci on chromosomes 10 and 18. The role of these loci in human hypertension remains to be determined. Other genes such as sodium-lithium countertransport may be involved. Environmental factors such as stress or salt intake could influence the rate or timing of expression of certain genes and thus result in hypertension.     

Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis. Its contribution to the development of cardiovascular diseases has long been recognized. Extensive literature has shown that peptides of the RAAS oscillate with a circadian periodicity in humans, under strong influence of posture, sleep, and age. Although observations of time-variant changes in the renin cascade are available in dogs, no detailed chronobiological investigation has been conducted so far. The present studies were designed to explore the circadian variations of plasma renin activity (RA) and urinary aldosterone-to-creatinine ratio (U_A:C) in relation to blood pressure (BP), sodium (U_Na, U_Na,fe), and potassium (U_K, U_K,fe) renal handling. Data derived from intensive blood and urine sampling, as well as continuous BP monitoring, were collected throughout a 24-h time period, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of day and night observations were compared by parametric statistics. Our results show that variables of the renin cascade, BP, and urinary electrolytes oscillate with significant day-night differences in dogs. An approximately 2-fold (1.6–3.2-fold) change between the average day and night measurements was found for RA (p?<?0.001), U_A:C (p?=?0.01), U_K,fe (p?=?0.01), and U_Na (p?=?0.007). Circadian variations in BP, albeit small (less than 10?mm Hg), were statistically significant (p?<?0.01) and supported by the model-based analysis. For all variables but U_Na and U_Na,fe, the levels were higher at night than during the day. The data also indicate that blood pressure oscillates in parallel to the RAAS, such that, as opposed to healthy humans, BP does not drop at night in dogs. The postprandial decrease in RA is assumed to be related to body fluid volume expansion secondary to water and sodium intake, whereas the reduction of U_A:C reflects aldosterone-stimulated secretion by the renin-angiotensin II pathway. U_Na and U_Na,fe peaked in the afternoon, about 7–8?h after food intake, which is consistent with the “impulse-response pattern” of sodium excretion described in previous publications. Finally, U_K and U_K,fe mirrored aldosterone-mediated potassium secretion in the kidney tubules. To describe the circadian variations of the various variables, two different mathematical representations were applied. A cosine model with a fixed 24-h period was found to fit the periodic variations of RA, U_A:C, U_K, U_K,fe, and BP well, whereas changes in U_Na and U_Na,fe were best characterized by a surge model. The use of nonlinear mixed effects allowed estimation of population characteristics that can influence the periodicity of the RAAS. Specifically, sodium intake was found to interact with the tonic and the phasic secretion of renin, suggesting that varying feeding time could also impact the chronobiology of the renin cascade. (Author correspondence: jonathan.mochel@novartis.com)     

High blood pressure. detection and treatment by general practitioners.

A questionnaire was sent to a 10% random sample of general practitioners in England and Wales on their attitudes to the detection and treatment of hypertension; 62% responded and no further inquiry was made. Their view on detection and criteria for treatment and investigations performed were considered in relation to their background. More of the older practitioners always measured blood pressure and 36% of all practitioners believed that hypertensive patients usually present with symptoms. Altogether 91% thought that strokes could be prevented by treating hypertension, and only 18% reported difficulty in keeping patients on treatment. Older practitioners preferred to measure the distolic pressure using phase five, while the younger preferred phase four. Nearly all doctors were satisfied with their current sphygmomanometers.     

Blood lead concentration,blood pressure,and renal function.

Blood lead concentrations were related to blood pressure and indicators of renal function in a clinical survey of 7735 middle aged men from 24 British towns. There was no overall evidence that blood lead concentrations were associated with systolic or diastolic blood pressure (r = +0.03 and +0.01, respectively). In the 74 men with a blood lead concentration of 1.8 mumol/l (37.3 micrograms/100 ml) or more there was some suggestion of increased hypertension, but this did not reach significance. Blood lead concentration did not have any relation with serum creatinine concentration. Moderate increases in blood lead concentration were associated with small increases in mean serum urate concentration and small decreases in mean serum urea concentration; these associations were both reduced when alcohol consumption was taken into account. There is no indication that exposure to lead at concentrations commonly encountered in British men is responsible for impaired renal function or increased blood pressure.