Influence of Changes of Blood Pressure on Vascular Angiotensin II Receptor Subtype Expression

Abstract

The evolving complexity associated with the renin-angiotensin cascade has been the focus of increasingly sophisticated pharmacological experimentation. The identification of at least 2 angiotensin II (Ang II) receptor subtypes led to functional subclassification of their activity. Activation of the type 1 (AT1) receptor is associated with the vasopressive and aldosterone-secreting effects of Ang II. Mice that lack the gene that encodes the AT2 receptor demonstrate normal development but an impaired drinking response to water deprivation and a reduction in spontaneous movements.1 Basal blood pressure is higher, and sensitivity to the pressor actions of exogenously delivered Ang II is increased.1,2 Differences in diastolic blood pressure persist even when AT1 receptors are blocked by losartan, indicating that this effect is independent of AT1. The greater pressor response to Ang II requires AT1 receptor activation and therefore, normally, AT2 receptors may serve to limit this.3 As a consequence, the concept of a vasodilator role for this receptor was introduced. See p 1006 Subsequently, a variety of reports have emerged linking the stimulation of AT2 with vasodilation in small resistance arteries in normotensive rats. The mechanism invoked usually is associated with nitric oxide (NO) production by endothelial cells and cGMP production …