Progesterone increases blood pressure in spontaneous gestational hypertension in rats.

BACKGROUND: Gestational hypertensive disorders are a leading cause of maternal mortality in the US, accounting for up to 10% of these deaths. During pregnancy, a new rat model (SHHF rat) has been shown to develop spontaneous hypertension with increases of more than 40 mm Hg systolic blood pressure (BP), which resolves after delivery, and which lead us to ask whether the hypertension may be triggered by increased levels of progesterone in these rats. METHODS: To test this hypothesis, groups of SHHF rats were treated with progesterone (PROG), estrogen (EST), or progesterone and estrogen (PROG+EST) that correspond to levels that occur during pregnancy. Control (CON) rats received saline-filled implants and pseudopregnancy was induced in another group. Wistar-Kyoto rats served as controls for SHHF rats. RESULTS: By experimental day 3, progesterone caused a significantly higher systolic BP, similar to pseudopregnancy and to previously reported values during pregnancy in this strain. Blood pressure in SHHF rats given estrogen was not significantly different. RU486 reversibly prevented the increase in BP induced by progesterone. CONCLUSIONS: These results indicate that an anomalous response to progesterone causes dramatic increases in BP in SHHF rats during a short period of time, in contrast to the decrease in BP in response to progesterone, which has been reported in other rat models of hypertension. An abnormal pressor response to progesterone should be considered a potential mechanism contributing to the development of hypertension during pregnancy.

Molecular mechanisms of reduced beta-adrenergic signaling in the aged heart as revealed by genomic profiling.

Myocardial aging leads to a reduction of beta-adrenergic receptor-induced metabolic and contractile responsiveness. We hypothesize that a change in the patterns of gene expression is important in these age-related events. To test this, hearts were harvested from young and aged male rats (3-4 and 20-22 mo, respectively). Total mRNA was extracted and prepared for hybridization to Affymetrix U34A GeneChips. Filtering criteria, involving fold change and a statistical significance cutoff were employed, yielding 263 probe pairs exhibiting differential signals. Of the 163 annotated genes, at least 56 (34%) were classified as signaling/cell communication. Of these 56, approximately half were directly involved in G protein-coupled receptor signaling pathways. We next determined which of these changes might be involved in anti-adrenergic activity and identified 19 potentially important gene products. Importantly, we observed a decrease in beta1-adrenergic receptor and adenylyl cyclase mRNAs, whereas the mRNA encoding beta-arrestin increased. Furthermore, the results demonstrate an increase in mRNAs encoding the adenosine A1 receptor and phospholipase D, which could increase anti-adrenergic effects. Moreover, the mRNAs encoding the muscarinic M3 receptor, nicotinic acetylcholine receptor beta3, and nicotinic acetylcholine receptor-related protein were increased as was the mRNA encoding guanylate kinase-associated protein. Interestingly, we also observed eight mRNAs whose abundance changed three- to sixfold with aging that could be considered as being compensatory. Although these results do not prove causality, they demonstrate that cardiac aging is associated with changes in the profiles of gene expression and that many of these changes may contribute to reduced adrenergic signaling.

The Jamaican hypertension prevalence study.

This study was designed to investigate the prevalence of hypertension in Jamaica. Jamaica has an area of 4,411 square miles and is divided into 14 parishes. The visited districts were randomly selected. The sample population was selected based upon a two-stage stratified random sampling design. Each dwelling in the "Sampling Universe" had an equal probability of being selected. The survey team spent a week in the districts in each parish selected. Employing the Statistical Institute of Jamaica's (STATIN) two-stage stratified random sampling design, preselected house-holds were visited. Non-response was documented and considered in the final analysis. Only individuals 15 years and older were allowed to participate in the study. The 2,064 subjects who participated were the basis for estimates of hypertension. Following logistic regression analysis, the main risk factors for hypertension are being female, advancing age, obesity, having diabetes and having a family history of hypertension. Jamaica has a point prevalence of hypertension of 30.8% in the 15-and-over age group. These findings would greatly assist in formulating policies to deal with this scourge of society.