Ureteral function is modulated by a local renin-angiotensin system.
OBJECTIVE
Although many aspects of ureteral physiology are well characterized, the exact mechanism of ureteral smooth muscle modulation has not been fully established. In other smooth muscle contractility is modulated by angiotensin II (AngII). We determined the presence of a local ureteral renin-angiotensin system and characterized the functional role of AngII in ureteral smooth muscle.


METHODS
Reverse transcriptase-polymerase chain reaction was performed to determine the expression of angiotensinogen, renin, angiotensin-converting enzyme and angiotensin receptor subtype 1 mRNA. The presence of AngII in ureteral tissue was determined by immunohistochemistry. Human and pig ureteral smooth muscle strips were suspended in tissue baths to determine the effect of the AngII receptor antagonist losartan on the frequency and amplitude of spontaneous ureteral contractions. Electrical field stimulation was performed before and after exposure to losartan.


RESULTS
Angiotensinogen, renin, angiotensin-converting enzyme and angiotensin receptor subtype 1 mRNA expression was detected in human ureter. Immunoreactivity for AngII was demonstrated in smooth muscle bundles and blood vessels of the ureter. Losartan decreased the amplitude and frequency of spontaneous ureteral contractions as well as the contractile response to electrical field stimulation in a dose dependent manner.


CONCLUSIONS
Gene expression of AngII precursors and receptor, and localization of AngII in the ureter suggest the presence of a local renin-angiotensin system in the ureter. The effect of AngII receptor antagonist on contractile responses suggests that AngII modulates ureteral smooth muscle contractile function. Therefore, a local renin-angiotensin system may have an important role in ureteral function under physiological and pathological conditions.
Santis
William F
WF
Division of Urology, Surgical Service, Veterans Affairs Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
Peters
Craig A
CA
Yalla
Subbarao V
SV
Sullivan
Maryrose P
MP
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014513:Ureter / Q000378:metabolism / Q000502:physiology
D000804:Angiotensin II; D019808:Losartan