Extrarenal renin and blood pressure regulation. An alternative viewpoint.
There is increasing evidence that a major site of production of angiotensin I and II is peripheral tissue. Both angiotensin I and II are present in venous blood in amounts far too high to be explained by their generation in blood alone, given the extensive conversion of angiotensin I to angiotensin II and clearance of both peptides across peripheral tissues. Much indirect evidence supports this argument for angiotensin production in tissues, and indicates that tissue production of angiotensin plays an important role in regulation of blood pressure. Tissue renin may represent uptake from plasma and/or local synthesis, but despite the ease with which renin-like activity can be measured in tissues, its interpretation is problematic because of interference by nonrenin enzymes and inadvertent activation of inactive renin. Moreover, given that enzymes other than renin are able to liberate angiotensin I and angiotensin II from angiotensinogen, there is no obligatory role for renin in angiotensin production in tissues. Inasmuch as tissue production is the major source of plasma angiotensin, the fall in plasma angiotensin levels after bilateral nephrectomy indicates that kidney-derived renin is the major contributor to tissue angiotensin production. This argument is supported by evidence that vascular renin-like activity is kidney-derived, and plays a dominant role in angiotensin-dependent pressor mechanisms. Near-normal levels of inactive renin in plasma of anephric subjects indicates extrarenal synthesis of inactive renin, and renin mRNA has been identified in various nonrenal tissues. Whether these tissues are also able to process inactive renin to active renin, and its role in local angiotensin production and blood pressure regulation, are currently being investigated.
Campbell
D J
DJ
St. Vincent's Institute of Medical Research, Victoria, Australia.
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D004285:Dogs; D006801:Humans; D051381:Rats; D012083:Renin / Q000502:physiology*; D012084:Renin-Angiotensin System; D014018:Tissue Distribution
D000804:Angiotensin II; D012083:Renin