Arteriolar constriction and local renin-angiotensin system in rat microcirculation

Area of Science:

• Physiology
• Pharmacology
• Cardiovascular Research

Background:

• The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in regulating blood pressure and fluid balance.
• Angiotensin converting enzyme (ACE) is a key enzyme in the RAAS, converting angiotensin I to angiotensin II, a potent vasoconstrictor.
• Understanding the local activity of ACE within specific tissues, like skeletal muscle microvasculature, is important for targeted therapeutic strategies.

Purpose of the Study:

• To investigate the role of local angiotensin converting enzyme (ACE) activity in the skeletal muscle microcirculation.
• To compare the vasoconstrictive effects of exogenously administered angiotensin I and tetradecapeptide renin substrate (TPSR) in isolated rat cremaster muscle.
• To evaluate the impact of ACE inhibition on vasoconstriction and the relative importance of circulating versus local renin and angiotensinogen.

Main Methods:

• Intravital microscopy was employed on isolated rat cremaster muscle preparations.
• The preparations were externally perfused to control for circulating enzymes and substrates.
• Vascular responses of second-, third-, and fourth-order arterioles to angiotensin I, TPSR, angiotensinogen, and renin were measured.
• The effect of the ACE inhibitor quinapril was assessed.

Main Results:

• Topical administration of angiotensin I and TPSR induced dose-dependent vasoconstriction in a stepwise manner across arteriole orders.
• The ACE inhibitor quinapril significantly attenuated vasoconstriction induced by both angiotensin I and TPSR.
• Angiotensinogen and renin alone caused minimal vasoconstriction in the absence of circulating factors.
• In normally perfused preparations, circulating renin and angiotensinogen elicited significant arteriolar constriction.

Conclusions:

• The skeletal muscle microvascular network exhibits significant local angiotensin converting enzyme activity, identifying it as a primary target for ACE inhibitors.
• The vasoconstrictive effects of TPSR differ from angiotensinogen, suggesting non-specific hydrolysis contributes to TPSR's action.
• Circulating renin and angiotensinogen are more potent inducers of arteriolar constriction in skeletal muscle microvasculature compared to local sources.