So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

https://www.cell.com/cell/pdf/S0092-8674(00)81573-1.pdf

A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy

Background We attempted to characterize age-related changes in blood pressure in both normotensive and untreated hypertensive subjects in a population-based cohort from the original Framingham Heart Study and to infer underlying hemodynamic mechanisms. Methods and Results A total of 2036 participants were divided into four groups according to their systolic blood pressure (SBP) at biennial examination 10, 11, or 12. After excluding subjects receiving antihypertensive drug therapy, up to 30 years of data on normotensive and untreated hypertensive subjects from biennial examinations 2 through 16 were used. Regressions of blood pressure versus age within individual subjects produced slope and curvature estimates that were compared with the use of ANOVA among the four SBP groups. There was a linear rise in SBP from age 30 through 84 years and concurrent increases in diastolic blood pressure (DBP) and mean arterial pressure (MAP); after age 50 to 60 years, DBP declined, pulse pressure (PP) rose steeply, and MA...

Hemodynamic Patterns of Age-Related Changes in Blood Pressure: The Framingham Heart Study

These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Significant changes in these guidelines include (1) the replacement of the term “prehypertension” with the term “elevated blood pressure,” (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.

Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents.

The small arteries play an important functional role in establishing the increased peripheral resistance found in essential hypertension. This paper concerns the direct measurement of the intrinsic mechanical and contractile properites of two categories of small arterial resistance vessels in the mesenteric bed of 5-month-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The vessels had mean internal diameters of 246 fim and 153 /*m when relaxed at 100 mm Hg effective transmural pressure. Segments (1 mm) were mounted in such a way that internal circumference could be controlled and the circumferential wall tension (T) measured. After mounting, each vessel was maximally activated (by K* depolarization at 37°C in the presence of 5 mM Ca) at an internal circumference for which AT was approximately maximal, where AT = Tactlve Trelaxed. From the average values of AT measured we have estimated (on the basis of Laplace's equation) that the SHR vessel would average values of AT measured we have estimated (on the basis of Laplace's equation) that the SHR vessels would have been able to contract against 34% greater pressures than the WKY vessels (P < 0.001). Optical measurements of the dimensions of these vessels showed a 23% greater wall thickness in the SHR vessels (P < 0.02). There were no significant differences in the calculated active wall stresses of the SHR and WKY vessels; this suggests that the greater contractility found in the SHR vessels may be due to their having a greater smooth muscle cell content. These vessel measurements have been examined as well as the rats' blood pressures and heart to body weight ratios. The comparison points to the possibility that the disturbance to the cardiovascular regulatory system which results in hypertension produces similar cellular responses in both the myocardium and the peripheral vasculature.

Contractile Properties of Small Arterial Resistance Vessels in Spontaneously Hypertensive and Normotensive Rats

Arterial pressure regulation: Overriding dominance of the kidneys in long-term regulation and in hypertension☆

Normal and sinoaortic baroreceptor-denervated dogs were monitored continuously (24 hours a day) to quantify the role of the baroreceptors in determining the average level and the variability of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance. The frequency of occurrence over 24-hour periods was obtained for each variable using a fiber optic curve-scanning system to read the variables from continuously recorded charts and a digital computer system to plot curves. The results indicate that the degree of hypertension previously reported for this preparation has been highly exaggerated, presumably due to the methods of study. The average 24-hour mean arterial blood pressure was 101.6 mm Hg in normal dogs and only 112.7 mm Hg in baroreceptor-denervated dogs. The normal dogs exhibited narrowly distributed 24-hour frequency distribution curves for blood pressure; in contrast the denervated dogs exhibited curves with twice the 24-hour standard deviation. Similar analysis indicated that the baroreceptors exerted less influence on the daily stabilization of heart rate than they did on arterial blood pressure and that they had very little if any influence on the daily stabilization of cardiac output and total peripheral resistance. Hemodynamic variables during postural changes were studied along with diurnal rhythms. We concluded that the primary function of the baroreceptor reflex is not to set the chronic level of arterial blood pressure but, instead, to minimize variations in systemic arterial blood pressure, whether these variations are caused by postural changes of the animal, excitement, diurnal rhythm, or even spontaneous fluctuations of unknown origin.

Role of the Baroreceptor Reflex in Daily Control of Arterial Blood Pressure and Other Variables in Dogs

Two concepts for the long-term regulation of arterial pressure were considered in this review, the neural control hypothesis and the volume regulation hypothesis. The role of the nervous system and fluid volume regulation are intertwined in a way that has made it difficult to experimentally evaluate their separate contributions in the long-term regulation of arterial pressure. Nevertheless, from a substantial body of work related to the neural control of cardiovascular function, it appears that the ability of the nervous system to control arterial pressure is limited to the detection and correction of rapid short-term changes of arterial pressure. A long and exhaustive search has yet yielded no new neural mechanisms beyond the classic sinoaortic baroreceptors that can detect changes of arterial pressure. The baroreceptor mechanisms are of great importance for the moment-to-moment stabilization of arterial pressure, but because they do not possess sufficient strength and because they reset in time to the prevailing level of arterial pressure, they cannot provide a sustained negative feedback signal to provide long-term regulation of arterial pressure in face of sustained stimuli. This is not to say that the nervous system cannot affect the long-term level of arterial pressure. A distinction is made here between the many factors that can influence the long-term level of pressure and those that actually serve to detect changes of pressure and serve to maintain the level of pressure within a narrow range over the period of our adult lifetime. In this sense, there is evidence that in genetically susceptible individuals, environmental stresses can influence the long-term level of arterial pressure via the central and peripheral neural autonomic pathways. It is inappropriate, however, to view the nervous system as a long-term controller of arterial pressure because there is yet no evidence that the CNS can detect changes of arterial pressure nor changes in total body sodium and water content over sustained periods whereby it could provide an adequate long-term normalization of such error signals. In contrast, evidence has grown in support of the renal pressure-diuresis volume regulation hypothesis for the long-term control of arterial pressure over the past decade. An enhanced understanding of the mechanisms of pressure diuresis-natriuresis coupled with studies exploring how changes of vascular volume can influence vascular smooth muscle tone provide a compelling basis for this hypothesis of long-term arterial pressure regulation. This overall concept is represented and summarized in Figure 12.(ABSTRACT TRUNCATED AT 400 WORDS)

Allen W. Cowley

Papers

Arterial pressure regulation: Overriding dominance of the kidneys in long-term regulation and in hypertension☆

Role of the Baroreceptor Reflex in Daily Control of Arterial Blood Pressure and Other Variables in Dogs

Long-term control of arterial blood pressure

Increased plasma arginine vasopressin levels in patients with congestive heart failure.

Brief Reviews: A Systems Analysis Approach to Understanding Long-Range Arterial Blood Pressure Control and Hypertension