About four weeks.

Depends on the dose of angiotensin you want to use. Subpressor doses produce hypertension after several days but pressor doses significantly increase blood pressure within the first 2 days. The best method I have tested is with osmotic mini pumps. This method release the drug with a constant and controlled flow. 

We have experience with the time and route of using angiotensin II infusion to induce hypertension in rats and mice. It all depends on how fast and how much you want the blood pressure going up. With respect to the doses, we infuse the pressor doses of angiotensin II at 60 ng/min for rats, and 40 ng/min for mice using alzet osmotic minipump model 2002 for 2 weeks, or model 2006 for 42 days. You can see blood pressure to increase significantly in 3 days after angiotensin II is infused. With respect to the route, we implant osmotic minipump subcutaneously in rats and intraperitoneally in mice. We have not had problems with these approaches. Hope this will answer your questions. 

Dear Dr. Sharma,

Many thanks for your questions. We saw marked increases (~40 mmHg) in blood pressure in 90% of in rats and mice with the doses mentioned. Body wt. may be a factor, of course. A dose of 60 ng/min for a rat of 250 g will mean about ~240 ng/kg/min, which is close to the dose you used. I'll expect that blood pressure would be increased to above 150 mmHg in most SD rats. In our cases, some rats may reach 140/150 mmHg, but many may reach 170 mmHg, with a mean value of about >160 mmHg after 2 week infusion. If you don't see bp increases in rats with your dose, you should check the quality of AngII compound, the way you prepared the AngII stock for infusion, and the location of the minipump you implanted etc. Hope this helps. Good luck.

Dear Dr. Sharma,

That is great to know that you have successfully established your angiotensin II-induced hypertension model. Angiotensin II-induced hypertension will last for a while after you stop the angiotensin II infusion. You may note that blood pressure will gradually decrease but it will take a week to fall to a level very likely (still slightly) higher than basal or control levels.

Hope that this helps and best wishes for your work.

Joe  

Hi Ravi,

My gut feeling is if you only got significant change in blood pressure on 28 days of angiotensin II infusion between two groups, then the change is "unlikely" due to the effect of the drug. It most likely due to the effect of withdrawal of angiotensin II infusion. We normally end the experiments one day before the pump is empty just to exclude this possibility.

We only used Model 2002 for 2 week infusion, which has produced consistent hypertension for us. We rarely use model 2004 or model 2006 for angiotensin II infusion, because as a peptide we worry that angiotensin II may be degraded substantially by week 4 or week 6. One option is to replace the pump with a new one every two weeks if you want better and consistent results.  

Good luck.

Joe