Antihypertensive Effect | ALNY Message Board Posts

Alnylam Pharmaceuticals

  ALNY website

  •  Registered Members of Investor Village:
    Please make sure you are signed in to your Investor Village account to enjoy the full benefits of our service and avoid the MediaPass paywall. If the MediaPass offer page is blocking you, click the light blue "No thanks, take me back" link on the middle right side of the form to get to our home page where you can sign in by entering your Investor Village User Name and Password. 

     MediaPass subscribers: Please make sure you are logged in to your MediaPass subscription to bypass the paywall. You can do this by clicking the light blue "Already have a MediaPass account? Login here" link on the middle left side of the subscription offer form and then entering the email address and password you used when you first signed up with MediaPass.  

    For assistance call 888-222-7309 or email

ALNY   /  Message Board  /  Read Message



Rec'd By
Authored By
Minimum Recs
Previous Message  Next Message   Post Message   Post a Reply return to message boardtop of board
Msg  34580 of 34849  at  5/14/2019 9:22:55 AM  by


Antihypertensive Effect

 Saw that Dirk tweeted this article.


Small interfering RNAs (siRNAs) targeting hepatic angiotensinogen (Agt) may provide long-lasting antihypertensive effects, but the optimal approach remains unclear. Here, we assessed the efficacy of a novel AGT siRNA in spontaneously hypertensive rats. Rats were treated with vehicle, siRNA (10 mg/kg fortnightly; subcutaneous), valsartan (31 mg/kg per day; oral), captopril (100 mg/kg per day; oral), valsartan+siRNA, or captopril+valsartan for 4 weeks (all groups, n=8). Mean arterial pressure (recorded via radiotelemetry) was lowered the most by valsartan+siRNA (−68±4 mm Hg), followed by captopril+valsartan (−54±4 mm Hg), captopril (−23±2 mm Hg), siRNA (−14±2 mm Hg), and valsartan (−10±2 mm Hg). siRNA and captopril monotherapies improved cardiac hypertrophy equally, but less than the dual therapies, which also lowered NT-proBNP (N-terminal pro-B-type natriuretic peptide). Glomerular filtration rate, urinary NGAL (neutrophil gelatinase-associated lipocalin), and albuminuria were unaffected by treatment. siRNA lowered circulating AGT by 97.9±1.0%, and by 99.8±0.1% in combination with valsartan. Although siRNA greatly reduced renal Ang (angiotensin) I, only valsartan+siRNA suppressed circulating and renal Ang II. This coincided with decreased renal sodium hydrogen exchanger type 3 and phosphorylated sodium chloride cotransporter abundances. Renin and plasma K+ increased with every treatment, but especially during valsartan+siRNA; no effects on aldosterone were observed. Collectively, these data indicate that Ang II elimination requires >99% suppression of circulating AGT. Maximal blockade of the renin-angiotensin system, achieved by valsartan+siRNA, yielded the greatest reduction in blood pressure and cardiac hypertrophy, whereas AGT lowering alone was as effective as conventional renin-angiotensin system inhibitors. Given its stable and sustained efficacy, lasting weeks, RNA interference may offer a unique approach to improving therapy adherence and treating hypertension.


     e-mail to a friend      printer-friendly     add to library      
| More
Recs: 1     Views: 124
Previous Message  Next Message   Post Message   Post a Reply return to message boardtop of board

Msg # Subject Author Recs Date Posted
34585 Re: Antihypertensive Effect evernewbliss 0 5/14/2019 4:53:52 PM

About Us  •  Contact Us  •  Follow Us on Twitter  •  Members Directory  •  Help Center  •  Advertise
Not a member yet? What are you waiting for? Create Account
Want to contribute? Support InvestorVillage by donating
© 2003-2019 All rights reserved. User Agreement
Financial Market Data provided by