An overview of essential hypertension in Americans as a multifactorial phenomenon: interaction of biologic and environmental factors.

This paper reviews the current literature on essential/primary hypertension in terms of its expression as a multifactorial phenomenon. The genetic and environmental risk factors involved in expression of hypertension and their interactions are discussed. A specific mutation in epithelial sodium channels, T549M, is presented as a genetic risk factor for primary hypertension as expression of this mutation has been reported to result in hyperabsorption of sodium in homozygous individuals. T549M is used in this report to illustrate the multifactorial nature of primary hypertension. Possible interactions of T549M with environmental factors known to promote hypertension and the outcome of these interactions are discussed. Data indicates that both genetic and environmental risk factors must be considered to understand and intervene effectively with patients who have primary or essential hypertension.

Staging of malignant cutaneous wounds: a pilot study.

PURPOSE/OBJECTIVES: To determine the color, size, hydration, and general appearance of malignant cutaneous wounds (MCWs); the effectiveness of using digital imagery to quantify wound characteristics; and the feasibility of an MCW staging system. DESIGN: Descriptive pilot study. SETTING: A university-affiliated, comprehensive cancer center. METHODS: Assessment of each subject's wound (N = 13) using the Hopkins Wound Assessment Tool (HWAT) and digital analysis of photographs. Development of an MCW staging system from grouping and classifying the assessment data. A panel of experts used the assessment data and MCW staging system to determine each subject's wound stage and the feasibility of a staging system. Visual HWAT data and digital photographic assessment data were compared for consistency in size, color, and hydration status. MAIN RESEARCH VARIABLES: Characteristics and stages of MCW; digital imagery. FINDINGS: Investigators identified four stages of MCW using the wound characteristics. Digitally assessed wound measurements of size, color, and hydration status were consistent, reflecting the ability of this method to accurately capture malignant wound characteristics. CONCLUSIONS: An MCW staging system is feasible. Wound color, hydration status, the absence or presence of nodules, drainage, pain, odor, and tunneling indicate the stage of malignant wound progression. The two stages identified are distinctly different from pressure or diabetic wound progression. Stage 1N is characterized by fibrous desmoplasia (hard fibrous nodule) of cancer metastasis, and stage 4 is characterized by destruction of the basement membrane. Data comparisons indicate that digital assessment has potential for more accurately recording wound assessment indices. IMPLICATIONS FOR NURSING PRACTICE: Nurses can improve their assessment and management of a patient's MCW by understanding the wounds' stages and using a digital imaging protocol. Further research is needed to establish the reliability and validity of the MCW staging system and the digital assessment and quantification protocol.

Terbutaline increases open channel density of epithelial sodium channel (ENaC) in distal lung.

Neonatal and adult vertebrate respiration is facilitated by alveolar fluid and sodium (Na+) absorption driven by apical sodium channels (ENaC). ENaC are characterized in Xenopus laevis lung (XLL) epithelia using voltage clamping and fluctuation analysis to non-invasively examine macroscopic transepithelial current and resistance (I(SC), R(T)), single channel current (i(Na)) and total channel density (N(T)) responses to a beta adrenergic agonist (Terbutaline). Terbutaline addition to the basolateral bath of XLL increased Na entry to > 200% of control reflecting a doubling of open channel density (N(o). These data are consistent with the notion that XLL can serve as a useful model for investigation of distal lung ENaC response to agents of physiological interest.

Insulin increases sodium (Na+) channel density in A6 epithelia: implications for expression of hypertension.

Essential or primary hypertension is a multifactorial disease that is expressed as a result of complex interactions between genes and environmental influences. Several mutations in many different proteins are associated with expression of hypertension, including abnormalities in the epithelial sodium channel (ENaC) found in absorptive organs (i.e., distal colon, distal tubule of the nephron). Some of these mutations result in structural and/or functional alterations in ENaC-mediated Na+ entry in epithelia responsible for fluid and electrolyte balance and are associated with expression of hypertension. Studies support the notion that there is a link between ENaC and hypertension of both the monogenic (single gene mutation) and primary or essential type (a multifactorial disease). Alterations of other aspects of the environment of absorptive cells (e.g., hyperinsulinemia, hyperaldosteronemia, high plasma cortisol, high plasma Na+) have also been shown to elicit hyperabsorption of Na+ via ENaC and therefore could contribute significantly to expression of hypertension in people with intermediate phenotypes. This article describes an initial study in which the effects of an environmental factor, extracellular levels of insulin, on ENaC were examined in a normal kidney cell model. Electrophysiologic techniques revealed that ENaC density rapidly increased in response to addition of insulin to the basolateral bath. This autoregulatory recruitment of Na+ total channel density masked a slight decrease in open channel probability. Insulin's effect on ENaC function and implications on fluid and electrolyte balance and expression of primary hypertension is discussed.

Steroid hormone-dependent expression of blocker-sensitive ENaCs in apical membranes of A6 epithelia.

Weak channel blocker-induced noise analysis was used to determine the way in which the steroids aldosterone and corticosterone stimulated apical membrane Na+ entry into the cells of tissue-cultured A6 epithelia. Among groups of tissues grown on a variety of substrates, in a variety of growth media, and with cells at passages 73-112, the steroids stimulated both amiloride-sensitive and amiloride-insensitive Na+ transport as measured by short-circuit currents in chambers perfused with either growth medium or a Ringer solution. From baseline rates of blocker-sensitive short-circuit current between 2 and 7 microA/cm2, transport was stimulated about threefold in all groups of experiments. Single channel currents averaged near 0.3 pA (growth medium) and 0.5 pA (Ringer) and were decreased 6-20% from controls by steroid due to the expected decreases of fractional transcellular resistance. Irrespective of baseline transport rates, the steroids in all groups of tissues stimulated transport by increase of the density of blocker-sensitive epithelial Na+ channels (ENaCs). Channel open probability was the same in control and stimulated tissues, averaging approximately 0.3 in all groups of tissues. Accordingly, steroid-mediated increases of open channel density responsible for stimulation of Na+ transport are due to increases of the apical membrane pool of functional channels and not their open probability.

Ca2+-sensing receptors in intestinal epithelium.

Expression of Ca2+-sensing receptors (CaR) was demonstrated in several human intestinal epithelial cell lines (T84, HT-29, and Caco-2) and in rat intestinal epithelium by both reverse transcriptase-polymerase chain reaction (PCR) and Northern blotting of RNA. Restriction patterns of the PCR products were of the sizes predicted by the human and rat sequences. CaR agonists (Ca2+, poly-L-arginine, protamine) mediated an increase in intracellular Ca2+ in HT-29-18-C1 cells (monitored by changes in fura 2 fluorescence), which was dependent on release from thapsigargin-sensitive stores. U-73122, an inhibitor of phosphatidylinositol-phospholipase C, eliminated the CaR agonist-mediated rise in intracellular Ca2+, whereas its inactive analog, U-73343, had no effect. Pertussis toxin pretreatment had no effect on CaR agonist-mediated modulation of intracellular Ca2+. Taken together, these studies demonstrate that CaR are expressed in intestinal epithelial cells and couple to mobilization of intracellular Ca2+. The presence of CaR in intestinal epithelial cells presents a new locus for investigations into the role(s) of extracellular Ca2+ in modulating intestinal epithelial cell differentiation and transepithelial Ca2+ transport.