Theoretical investigations of intercellular communication in the microcirculation: Conducted responses, myoendothelial projections and endothelium derived hyperpolarizing factor

The contractile state of microcirculatory vessels is a major determinant of the blood pressure of the whole systemic circulation. Continuous bi-directional communication exists between the endothelial cells (ECs) and smooth muscle cells (SMCs) that regulates calcium (Ca2+) dynamics in these cells. This study presents theoretical approaches to understand some of the important and currently unresolved microcirculatory phenomena. ^ Agonist induced events at local sites have been shown to spread long distances in the microcirculation. We have developed a multicellular computational model by integrating detailed single EC and SMC models with gap junction and nitric oxide (NO) coupling to understand the mechanisms behind this effect. Simulations suggest that spreading vasodilation mainly occurs through Ca 2+ independent passive conduction of hyperpolarization in RMAs. Model predicts a superior role for intercellular diffusion of inositol (1,4,5)-trisphosphate (IP3) than Ca2+ in modulating the spreading response. ^ Endothelial derived signals are initiated even during vasoconstriction of stimulated SMCs by the movement of Ca2+ and/or IP3 into the EC which provide hyperpolarizing feedback to SMCs to counter the ongoing constriction. Myoendothelial projections (MPs) present in the ECs have been recently proposed to play a role in myoendothelial feedback. We have developed two models using compartmental and 2D finite element methods to examine the role of these MPs by adding a sub compartment in the EC to simulate MP with localization of intermediate conductance calcium activated potassium channels (IKCa) and IP3 receptors (IP 3R). Both models predicted IP3 mediated high Ca2+ gradients in the MP after SMC stimulation with limited global spread. This Ca 2+ transient generated a hyperpolarizing feedback of ∼ 2–3mV. ^ Endothelium derived hyperpolarizing factor (EDHF) is the dominant form of endothelial control of SMC constriction in the microcirculation. A number of factors have been proposed for the role of EDHF but no single pathway is agreed upon. We have examined the potential of myoendothelial gap junctions (MEGJs) and potassium (K+) accumulation as EDHF using two models (compartmental and 2D finite element). An extra compartment is added in SMC to simulate micro domains (MD) which have NaKα2 isoform sodium potassium pumps. Simulations predict that MEGJ coupling is much stronger in producing EDHF than alone K+ accumulation. On the contrary, K+ accumulation can alter other important parameters (EC V m, IKCa current) and inhibit its own release as well as EDHF conduction via MEGJs. The models developed in this study are essential building blocks for future models and provide important insights to the current understanding of myoendothelial feedback and EDHF.^

The Effect of Carbohydrate Amount, Quality and Type on Arterial Pulse Pressure in Cuban-Americans with and Without Type 2 Diabetes

Background: Arterial pulse pressure, the difference between systolic and diastolic blood pressure, has been used as an indicator (surrogate measure) of arterial stiffness. High arterial pulse pressure (> 40) has been associated with increased cardiovascular disease and mortality. Several clinical trials have reported that the proportion of calories from carbohydrate has an effect on blood pressure. The primary objective of this study was to assess arterial pulse pressure and its association with carbohydrate quantity and quality (glycemic load) with diabetes status for a Cuban American population. Methods: A single point analysis included 367 participants. There was complete data for 365 (190 with and 175 without type 2 diabetes). The study was conducted in the investigator’s laboratory located in Miami, Florida. Demographic, dietary, anthropometric and laboratory data were collected. Arterial pulse pressure was calculated by the formula systolic minus the diastolic blood pressure. Glycemic load, fructose, sucrose, percent of average daily calories from carbohydrate, fat and protein, grams of fiber and micronutrient intakes were calculated from a validated food frequency questionnaire. Results: The mean arterial pulse pressure was significantly higher in participants with (52.9 ± 12.4) than without (48.6 ± 13.4) type 2 diabetes. The odds of persons with diabetes having high arterial pulse pressure (>40) was 1.85 (95% CI =1.09, 3.13); p=0.023. For persons with type 2 diabetes higher glycemic load was associated with lower arterial pulse pressure. Conclusions: Arterial pulse pressure and diet are modifiable risk factors of cardiovascular disease. Arterial pulse pressure may be associated with carbohydrate intake differently considering diabetes status. Results may be due to individuals with diabetes following dietary recommendations. The findings of this study suggest clinicians take into consideration how medical condition, ethnicity and diet are associated with arterial pulse pressure before developing a medical nutrition therapy plan in collaboration with the client.

Phylloquinone (Vitamin K₁) Intake and Pulse Pressure as a Measure of Arterial Stiffness in Older Adults

This study examined the relationships among ethnicity/race, lifestyle factors, phylloquinone (vitamin K₁) intake, and arterial pulse pressure in a nationally representative sample of older adults from four ethnic/racial groups: non-Hispanic Whites, non-Hispanic Blacks, Mexican Americans, and other Hispanics. This was a cross-sectional study of U.S. representative sample with data from the National Health and Nutrition Examination Surveys, 2007-2008 and 2009-2010 of adults aged 50 years and older (N = 5296). Vitamin K intake was determined by 24-hour recall. Pulse pressure was calculated as the difference between the averages of systolic blood pressure and diastolic blood pressure. Compared to White non-Hispanics, the other ethnic/racial groups were more likely to have inadequate vitamin K₁ intake. Inadequate vitamin K₁ intake was an independent predictor of high arterial pulse pressure. This was the first study that compared vitamin K₁ inadequacy with arterial pulse pressure across ethnicities/races in U.S. older adults. These findings suggest that vitamin K screening may be a beneficial marker for the health of older adults.