The mode of blood pressure inheritance and some genetic markers of spontaneous hypertension were evaluated in a new set of recombinant inbred (RI) strains obtained by crossing of normotensive (BN.lx) and hypertensive (SHR) progenitor strains. Blood pressure values of RI strains were continuously distributed between both progenitor strains, although normotensive strains slightly prevailed. Statistical analysis suggested that there are three major genes and multiple minor genes responsible of the determination of spontaneous hypertension. The association between blood pressure and gene(s) within RT1 complex or gene(s) closely linked to it was found by RI strain analysis. This suggestion was confirmed by the detection of significant difference in blood pressure between SHR and SHR.1N congenic strains. Our results indicate that RT1 complex gene(s) may be involved in the development of high blood pressure.

In this review, we attempt to outline the age-dependent interactions of principal systems controlling the structure and function of the cardiovascular system in immature rats developing hypertension. We focus our attention on the cardiovascular effects of various pharmacological, nutritional, and behavioral interventions applied at different stages of ontogeny. Several distinct critical periods (developmental windows), in which particular stimuli affect the further development of the cardiovascular phenotype, are specified in the rat. It is evident that short-term transient treatment of genetically hypertensive rats with certain antihypertensive drugs in prepuberty and puberty (at the age of 4–10 wk) has long-term beneficial effects on further development of their cardiovascular apparatus. This juvenile critical period coincides with the period of high susceptibility to the hypertensive effects of increased salt intake. If the hypertensive process develops after this critical period (due to early antihypertensive treatment or late administration of certain hypertensive stimuli, e.g., high salt intake), blood pressure elevation, cardiovascular hypertrophy, connective tissue accumulation, and end-organ damage are considerably attenuated compared with rats developing hypertension during the juvenile critical period. As far as the role of various electrolytes in blood pressure modulation is concerned, prohypertensive effects of dietary Na⁺and antihypertensive effects of dietary Ca²⁺are enhanced in immature animals, whereas vascular protective and antihypertensive effects of dietary K⁺are almost independent of age. At a given level of dietary electrolyte intake, the balance between dietary carbohydrate and fat intake can modify blood pressure even in rats with established hypertension, but dietary protein intake affects the blood pressure development in immature animals only. Dietary protein restriction during gestation, as well as altered mother-offspring interactions in the suckling period, might have important long-term hypertensive consequences. The critical periods (developmental windows) should be respected in the future pharmacological or gene therapy of human hypertension.

Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin–angiotensin–aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine.

It has recently been proposed that sequence variation in the gene coding for tissue kallikrein might be involved in the pathogenesis of hypertension. However, molecular evidence of an association between a sequence alteration in the kallikrein gene family and the transmission of increased blood pressure has never been reported. In 32 recombinant inbred (RI) strains derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway rat (BN), we investigated whether a restriction fragment length polymorphism (RFLP) marking the kallikrein gene family cosegregated with blood pressure. In the RI strains that inherited the kallikrein RFLP from the SHR progenitor strain, the median systolic, diastolic, and mean arterial pressures were significantly greater than in the RI strains that inherited the kallikrein RFLP from the BN progenitor strain. These findings suggest that in the rat, sequence variation in the kallikrein gene family, or in closely linked genes, may have the capacity to affect blood pressure.

Essential hypertension is a major risk factor for several cardiovascular diseases. It is a complex trait resulting from the interactions of multiple genetic and environmental factors. Moreover, not only genetic but also epigenetic inheritance plays a significant role. One can speculate that hypertension develops as a consequence of “errors” in well-coordinated regulatory systems of blood pressure. Errors in the cascade of molecular, biochemical and genetic processes, which regulate blood pressure, have finally enough potential to result in hypertension. Numerous environmental factors surrounding the organism during its development should influence the expression of genetic information. However, despite the considerable research effort, it is still difficult to identify all genes and/or other genetic determinants leading to essential hypertension and other cardiovascular diseases. This is mainly because these diseases usually become a medical problem in adulthood, although their roots might be traced back to earlier stages of ontogeny. The link between distinct developmental periods (e.g. birth and adulthood) should involve changes in gene expression involving epigenetic phenomena. The purpose of the present paper is to bring a piece of light on gene-environmental interactions potentially implicated in the pathogenesis of hypertension.

To assess the influence of environmental temperature on blood pressure, we analyzed 42,813 readings of systolic and diastolic blood pressures in recumbent and upright positions in 2,000 hypertensive patients in our clinic in correlation to noon temperature and mean daily temperature in Montréal. The sample comprised 860 men and 1140 women with an average age of 55 years. Analysis of variance showed highly statistically significant negative correlations for all blood pressure values between different noon temperature, as well as mean daily temperature, groups. The greatest difference for systolic blood pressure was 7 mm Hg, and for diastolic blood pressure it was 3 mm Hg, within the – 24 °C to 27°C temperature range. The same relationship between blood pressure and different environmental temperatures was also seen when the blood pressure recordings were divided between temperature below 0°C and above 0°C, ie, within the winter or summer months. This environmental effect may have a clinically significant impact because thermosensitivity appears to be related to hypertension Am J Hypertens 1991;4:422-426