Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice.

Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD (CDPRR-KO). At basal conditions, CDPRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na+ excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg-1·min-1), the increases in systolic BP and diastolic BP were mitigated in CDPRR-KO mice. CDPRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and renin content in urine compared with wild-type mice. In isolated CD from CDPRR-KO mice, patch-clamp studies demonstrated that ANG II-dependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments.

Clinical Case of the Month: A 49-Year-Old Man with Fever, Headache and Leg Weakness.

A 49-year-old man with an unremarkable past medical history presented to an outside hospital with a five-day history of fever, left leg weakness, myalgia and headache. The patient reported that the illness started as a fever and sore throat and he was originally diagnosed with streptococcal pharyngitis and prescribed antibiotics. The day after his initial diagnosis, his fever had progressed to include a headache, myalgia, a rash on his upper torso and right shoulder and sudden-onset left leg weakness with preserved sensation. With progressively worsening symptoms, he eventually presented to a local emergency department (ED), five days after his symptoms first started. He was experiencing continued left leg weakness, an inability to ambulate, persistent fevers to 103ºF, muscle aches, an intense band-like headache and confusion. The patient denied neck stiffness, photophobia, loss of sensation or any additional muscle weakness. He denied any recent travel aside from work, any sick contacts, recent tick/insect bites, history of sexually transmitted diseases or contact with animals. He reported no history of illicit drug use as well as no recent weight loss, trauma or radiation exposure. The patient had approximately a 10-pack-year tobacco smoking history. For the last ten years he drank about a six-pack of beer daily while onshore (roughly two weeks out of every month). He works on an offshore oil platform. He was not taking any home medications besides his recently prescribed antibiotics. He lived alone at home in a moderately rural area of South Louisiana. His family history was non-contributory.