Home
home page for the UCSD hypertension program

Program
UCSD hypertension program

Objectives
program aims and
objectives

Organization
program organization

Projects and Cores
program projects and
cores, with relations
to program strategies

Flow Chart
program flow chart

Personnel
program personnel

UCSD NHLBI Program

Sympathetic Neuroeffector Junctions and Blood Pressure

Human Essential Hypertension

Description of UCSD Program

The following briefly describes the UCSD program to study human essential hypertension.

Introduction:

The sympathetic branch of the autonomic system is a key regulator of blood pressure. Secretory vesicles of chromaffin cells and sympathetic axons release co-stored transmitters by exocytosis into the bloodstream or synaptic clefts, where they contact cardiovascular target cells. In addition to catecholamines, the secretory "quantum" includes neuropeptides (such as NPY; Project 3), and chromogranins, precursors of active peptides which influence vascular responses to sympathoadrenal activation, and hence blood pressure.

The Program:

This Program links four Projects and five Core Facilities (see Flow Chart) with long-standing collaborations in synthesis, release, and actions (pre- and post-synaptic) of these transmitters, integrating their effects on blood pressure. Central hypotheses and themes focus interactive efforts. Projects 1 and 2 include human studies, and Project 2 probes sympathetic neuroeffector mechanisms in intact rodents, while Projects 4 and 2 clarify cellular mechanisms in transmitter biosynthesis and release, and also exploit ex vivo biological materials from Projects 1 and 2 for phenotyping. Human studies probe the genetic basis of heritable alterations in autonomic activity in pedigrees with hypertension (Project 1; Core D), and each Project (1 and 4) participates in phenotyping unique autonomic traits in pedigree members. Significant, novel genetic linkages have already emerged, with intriguing allelic variations found in the alpha-1-beta-adrenergic receptor and the renal kallikrein promoter.

The five Core facilities provide defined cell populations, signal probes, genotyping, physical mapping, informatics, catecholamine and vasoactive peptide assays, and imaging. Using molecular biological and informatics tools, the program aims to achieve a new level of understanding of the dynamic complexity of the sympathetic neuroeffector junction, and how its components contribute to heritable changes in blood pressure, and ultimately to human hypertension.

Latest modification: December, 1999

If you have comments or queries, send email to Doug Smith