Vasoconstriction is determined by interstitial rather than circulating angiotensin II.

Area of Science:

• Cardiovascular Physiology
• Renal Physiology
• Pharmacology

Background:

• Angiotensin (Ang) I and Angiotensin (Ang) II are key regulators of blood pressure.
• Despite Ang II being the primary active peptide, Ang I and Ang II exhibit similar potencies in inducing vasoconstriction.
• The mechanism behind this similar potency, given limited Ang I to Ang II conversion, remains unclear.

Purpose of the Study:

• To investigate the reasons for similar vasoconstrictive potencies of Ang I and Ang II.
• To determine whether differing AT receptor populations or local Ang II generation contribute to the observed potencies.
• To elucidate the role of interstitial versus circulating Ang II in mediating vasoconstriction.

Main Methods:

• Concentration-response curves for Ang I and Ang II were generated in porcine femoral arteries.
• Experiments were conducted with and without AT(1) and AT(2) receptor antagonists (irbesartan and PD123319).
• Ang I, Ang II, and metabolite levels were measured in both bath fluid and tissue during vasoconstriction.

Main Results:

• The potency difference between Ang I and Ang II was approximately 2-fold, not explained by different AT receptor stimulation.
• Bath fluid Ang II levels were significantly lower during Ang I application compared to Ang II application.
• Interstitial Ang II levels, calculated from tissue and bath fluid measurements, showed only a 2-4 fold difference between Ang I and Ang II, suggesting interstitial Ang II is the primary mediator of vasoconstriction.

Conclusions:

• Interstitial Ang II levels, rather than circulating levels, are the primary determinant of vasoconstriction.
• Local conversion of Ang I to Ang II within the arterial wall by angiotensin-converting enzyme (ACE) generates significant interstitial Ang II.
• Arterial Ang I may be physiologically more important than arterial Ang II due to its efficient local conversion to potent interstitial Ang II.