Accurate measurement of blood pressure is essential to classify individuals, to ascertain blood pressure-related risk, and to guide management. The auscultatory technique with a trained observer and mercury sphygmomanometer continues to be the method of choice for measurement in the office, using the first and fifth phases of the Korotkoff sounds, including in pregnant women. The use of mercury is declining, and alternatives are needed. Aneroid devices are suitable, but they require frequent calibration. Hybrid devices that use electronic transducers instead of mercury have promise. The oscillometric method can be used for office measurement, but only devices independently validated according to standard protocols should be used, and individual calibration is recommended. They have the advantage of being able to take multiple measurements. Proper training of observers, positioning of the patient, and selection of cuff size are all essential. It is increasingly recognized that office measurements correlate poorly with blood pressure measured in other settings, and that they can be supplemented by self-measured readings taken with validated devices at home. There is increasing evidence that home readings predict cardiovascular events and are particularly useful for monitoring the effects of treatment. Twenty-four-hour ambulatory monitoring gives a better prediction of risk than office measurements and is useful for diagnosing white-coat hypertension. There is increasing evidence that a failure of blood pressure to fall during the night may be associated with increased risk. In obese patients and children, the use of an appropriate cuff size is of paramount importance.

/pdf/recommendations-for-blood-pressure-measurement-in-humans-and-19z5w6eq69.pdf

Recommendations for Blood Pressure Measurement in Humans and Experimental Animals Part 1: Blood Pressure Measurement in Humans: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research

Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.

/pdf/estrogen-receptors-and-human-disease-4qaa439dla.pdf

Estrogen receptors and human disease

Cardiovascular diseases (CVDs), the major cause of morbidity and mortality for both men and women, occur uncommonly in premenopausal women, but their incidence rises sharply after the menopausal transition. Cardiovascular gender differences are apparent long before CVDs appear in men and women, and improved understanding of the biology underlying these differences has the potential to advance the diagnosis and treatment of CVDs in both sexes. This review considers gender differences in the molecular and cellular physiology of the heart and blood vessels in health and disease, highlighting understudied areas that can help resolve the current controversy regarding hormone replacement therapy and improve cardiovascular health in women.

https://science.sciencemag.org/content/sci/308/5728/1583.full.pdf

Molecular and cellular basis of cardiovascular gender differences

In experimental animals, as in humans, techniques for measuring blood pressure (BP) have improved considerably over the past decade. In this document, we present recommendations for measuring BP in experimental animals with the goal of helping investigators select optimal methods for BP monitoring in the research laboratory. The advantages and disadvantages of various BP measurement methods are discussed and specific recommendations are provided for selecting the optimal technique depending on the study objective. Although indirect techniques that permit only sporadic measurements of BP may be suitable for some purposes, methods for directly measuring BP are generally preferred because of their ability to monitor the highly dynamic nature of BP in a comprehensive fashion. Selection of the methods to be used should ultimately be guided by the study objectives to insure that the techniques chosen are appropriate for the experimental questions being explored.

Recommendations for Blood Pressure Measurement in Humans and Experimental Animals: Part 1: Blood Pressure Measurement in Humans: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research

Potassium-selective channels are the largest and most diverse group of ion channels, represented by some 70 known loci in the mammalian genome. The first cloned potassium channel gene was the Drosophila voltage-gated shaker channel, and this was rapidly followed by the identification of other

https://pharmrev.aspetjournals.org/content/pharmrev/57/4/473.full.pdf

International Union of Pharmacology. LIII. Nomenclature and Molecular Relationships of Voltage-Gated Potassium Channels

Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor beta (ERbeta)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERbeta-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERbeta-deficient mice. Vascular smooth muscle cells isolated from ERbeta-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERbeta-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERbeta in the regulation of vascular function and blood pressure.

https://science.sciencemag.org/content/sci/295/5554/505.full.pdf

Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β

We report here a combination of site-directed mutations that eliminate the high-affinity Ca(2+) response of the large-conductance Ca(2+)-activated K(+) channel (BK(Ca)), leaving only a low-affinity response blocked by high concentrations of Mg(2+). Mutations at two sites are required, the "Ca(2+) bowl," which has been implicated previously in Ca(2+) binding, and M513, at the end of the channel's seventh hydrophobic segment. Energetic analyses of mutations at these positions, alone and in combination, argue that the BK(Ca) channel contains three types of Ca(2+) binding sites, one of low affinity that is Mg(2+) sensitive (as has been suggested previously) and two of higher affinity that have similar binding characteristics and contribute approximately equally to the power of Ca(2+) to influence channel opening. Estimates of the binding characteristics of the BK(Ca) channel's high-affinity Ca(2+)-binding sites are provided.

https://rupress.org/jgp/article-pdf/120/2/173/1147747/jgp1202173.pdf

Elimination of the BKCa Channel's High-Affinity Ca2+ Sensitivity

There is controversy over whether Ca2+ binds to the BKCa channel's intracellular domain or its integral-membrane domain and over whether or not mutations that reduce the channel's Ca2+ sensitivity act at the point of Ca2+ coordination. One region in the intracellular domain that has been implicated in Ca2+ sensing is the “Ca2+ bowl”. This region contains many acidic residues, and large Ca2+-bowl mutations eliminate Ca2+ sensing through what appears to be one type of high-affinity Ca2+-binding site. Here, through site-directed mutagenesis we have mapped the residues in the Ca2+ bowl that are most important for Ca2+ sensing. We find acidic residues, D898 and D900, to be essential, and we find them essential as well for Ca2+ binding to a fusion protein that contains a portion of the BKCa channel's intracellular domain. Thus, much of our data supports the conclusion that Ca2+ binds to the BKCa channel's intracellular domain, and they define the Ca2+ bowl's essential Ca2+-sensing motif. Overall, however, we have found that the relationship between mutations that disrupt Ca2+ sensing and those that disrupt Ca2+ binding is not as strong as we had expected, a result that raises the possibility that, when examined by gel-overlay, the Ca2+ bowl may be in a nonnative conformation.

https://rupress.org/jgp/article-pdf/123/5/475/1220410/jgp1235475.pdf

Mapping the BKCa Channel's “Ca2+ Bowl”: Side-chains Essential for Ca2+ Sensing

https://www.cell.com/biophysj/pdf/S0006-3495(08)70722-7.pdf

Lin Bao

Papers

Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β

Elimination of the BKCa Channel's High-Affinity Ca2+ Sensitivity

Mapping the BKCa Channel's “Ca2+ Bowl”: Side-chains Essential for Ca2+ Sensing

Modulation of the Conductance-Voltage Relationship of the BKCa Channel by Mutations at the Putative Flexible Interface between Two RCK Domains