Life and death in the microcirculation: a role for angiotensin II

Objective: Angiotensin II (ANGII) plays a critical role in the maintenance of the microcirculation and in the anatomical loss of microvessels (rarefac tion) that occurs in low renin forms of hypertension and in animals fed a h igh-salt diet. Elevations in sodium intake can trigger a series of hemodyna mic and hormonal responses culminating in a substantial rarefaction of smal l arterioles and capillaries in both normal and reduced renal mass hyperten sive rats. Methods: Immunohistochemistry, Northern blot, and reverse transcription-pol ymerase chain reaction (RT-PCR) analysis of microdissected blood vessels we re used to localize ANGII receptors in the microcirculation. Chronic infusi on of ANGII and other physiologic and pharmacologic manipulations of the re ninangiotensin system in rats was combined with morphologic and mathematica l analysis of the network architecture. Results: We have shown that rarefaction of the microcirculation can cause a n increase in total peripheral resistance, reduced tissue perfusion, decrea sed oxygen delivery, and impaired organ function. Although the mechanisms b y which this occurs are not well understood, a number of key observations p oint to a role for the renin-angiotensin system in this effect. First, ANGI I infused systemically at subpressor levels, or locally into the skeletal m usic interstitium, can induce significant microvessel growth. Second, local ization of ANGII receptor proteins by immunohistochemistry and Western blot ting and RNA localization by RT-PCR confirm the presence of AT(1) receptors , which are growth-stimulatory, and AT(2) receptors, which ale growth-inhib itory in the microcirculation. Third, maintenance of ANGII at normal levels during periods of hypertension or high-salt diet completely eliminates rar efaction. Conclusions: Taken together, these results support the hypothesis that ANGI I acting through AT(1)- and AT(2)-receptor mechanisms modulate vessel densi ty during high-salt diet and hypertension.