The greater renin system. Its prorenin-directed vasodilator limb. Relevance to diabetes mellitus, pregnancy, and hypertension.
A greater renin system is proposed. Evidence is presented that a greater renin system exists that has both vasodilator and vasoconstrictor properties. Vasodilator activity is induced by prorenin, vasoconstrictor activity by renin. Our model is based on evidence that both prorenin and renin have the capacity to generate angiotensin and that angiotensin causes vasodilation at high concentrations and vasoconstriction at low concentrations. In our model, prorenin acts only at particular target sites while renin of renal origin acts via the general circulation. Prorenin's designation as a biosynthetic precursor implies lack of intrinsic catalytic activity whereas in fact it can become reversibly active. Activation may occur in vivo at binding sites without cleavage of the prosequence. In this framework, prorenin should be more aptly called renin I and circulating active renin, renin II. In our model, the role of renin I (prorenin) is to generate localized high concentrations of angiotensin II, eg, in the afferent arteriole of the kidney and in other vital organs, causing regional dilation by rendering tissues insensitive (tachyphylactic) to the vasoconstrictor effect of circulating angiotensin II or by releasing vasodilator substances. The role of renin II (active renin) is to constrict resistance vessels and the efferent arteriole of the kidney, thereby raising blood pressure, maintaining glomerular filtration rate, and enabling more blood flow to those organs that selectively bind prorenin. This twin control system is ideally designed to maintain blood flow to vital organs.(ABSTRACT TRUNCATED AT 250 WORDS)
Sealey
J E
JE
Cardiovascular Center, Cornell University Medical College, New York, New York 10021.
von Lutterotti
N
N
Rubattu
S
S
Campbell
W G
WG
Gahnem
F
F
Halimi
J M
JM
Laragh
J H
JH
D000804:Angiotensin II / Q000502:physiology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004792:Enzyme Precursors / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D012083:Renin / Q000235:genetics / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D004792:Enzyme Precursors; D000804:Angiotensin II; D012083:Renin