Reninlike enzymes in human vasculature

Area of Science:

• Biochemistry
• Cardiovascular Physiology
• Hypertension Research

Background:

• Angiotensin I (Ang I)-forming enzymes are crucial in the renin-angiotensin system.
• Previous theories suggested stimulation of these enzymes in essential hypertension.
• Understanding extrarenal sources of Ang I is vital for cardiovascular health.

Purpose of the Study:

• To identify Ang I-forming angiotensinogenases in human extrarenal vasculature.
• To investigate the theory of Jiménez Días regarding their stimulation in essential hypertension.
• To characterize the activity and distribution of these enzymes.

Main Methods:

• Enzyme-kinetic assays using Ang I radioimmunoassay and purified angiotensinogens.
• Analysis of vascular sections from normotensive and hypertensive patients, umbilical cords, explanted hearts, and serum.
• Determination of pH optima for identified enzymes.

Main Results:

• Three nonrenin Ang I-forming angiotensinogenases with distinct pH optima were identified in extrarenal vasculature, cardiac tissue, and plasma.
• Highest activities were observed in cardiac tissue, followed by carotid artery intima and other arteries.
• Extrarenal arterial enzyme activities showed linear correlation with local angiotensin-converting enzyme and plasma renin activity.
• Essential hypertension did not exhibit general stimulation of these enzymes.

Conclusions:

• Nonrenin Ang I-forming angiotensinogenases exist in human extrarenal vasculature, kidney, and plasma.
• The theory of stimulated extrarenal arterial Ang I-forming angiotensinogenases in essential hypertension is not supported by this data.
• A classification system for Ang I-forming angiotensinogenase activity in hypertension is proposed, categorizing patients into high, normal, or low activity subgroups.