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During this era of rapidly expanding information about the physiology of biologic systems, it remains important that we attempt to assimilate new discoveries with past observations, particularly when the historical findings are implicated in disease processes. As we proceed with the assimilation process and make previously unrecognized connections between old facts and new discoveries, we sometimes find that they mesh neatly together and provide a new framework for understanding phenomena that were, previously, only poorly understood. With this in mind, the goal of the present paper is to describe how our knowledge of historical data linking whole-animal Ca homeostasis with vascular reactivity and blood pressure (BP) takes on new dimensions when considered in terms of recent advances showing that Ca serves as a primary signal to modulate cell function. Specifically, we have formulated a novel hypothesis that potentially explains the molecular connection between Ca homeostasis and BP, clarifies decades-old observations regarding vascular reactivity that were poorly understood, and provides new avenues for critical hypothesis testing. Of note, as this paper is not intended to be a literature review, no attempt has been made to be inclusive in citation of the literature; rather, in most instances, only seminal reports or other pertinent advances are cited. THE HYPOTHESIS

The perivascular sensory nerve Ca2+ receptor and blood pressure regulation *1A hypothesis