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Chronic AT1 receptor blockade alters aortic nerve activity in hypertension
C M dos Santos1, E D Moreira, E M Krieger
1Department of Physiology and Biophysics, ICB, São Paulo, SP, Brazil.
Insights
Angiotensin II blockade with losartan improved baroreceptor sensitivity in coarctation hypertension. This suggests angiotensin II contributes to reduced baroreceptor gain in this condition.
Area of Science:
- Cardiovascular Physiology
- Hypertension Research
- Neuropharmacology
Background:
- Coarctation hypertension (CH) is associated with reduced baroreceptor sensitivity.
- Previous studies showed normalization of heart rate reflex control with losartan treatment in CH.
- The role of angiotensin II in afferent aortic nerve activity in CH requires further investigation.
Purpose of the Study:
- To analyze the effects of angiotensin II blockade on afferent aortic nerve activity in chronic coarctation hypertension.
- To determine if angiotensin II influences baroreceptor sensitivity independently of its pressure-lowering effects.
Main Methods:
- Rats with coarctation hypertension (CH) or sham-operated controls received chronic vehicle or losartan treatment.
- Aortic pressure and aortic nerve activity were recorded in conscious and anesthetized rats.
- The aortic nerve activity/pressure relationship was analyzed to assess baroreceptor sensitivity.
Main Results:
- Losartan treatment reduced blood pressure in CH rats.
- Coarctation significantly increased pressure and depressed aortic nerve activity/pressure relationship.
- Losartan treatment significantly attenuated this depression and reduced afferent discharge variability.
Conclusions:
- Angiotensin II, via AT1 receptors, decreases aortic afferent nerve sensitivity during physiological pressure fluctuations.
- Angiotensin II contributes to the reduced baroreceptor gain observed in chronic hypertension.
- Targeting angiotensin II may be a therapeutic strategy for improving baroreceptor function in CH.
Abstract:
In the chronic phase of coarctation hypertension (CH) we have shown both reduction in baroreceptor sensitivity (Hypertension. 1992;19[suppl II]:II-198-II-201.) and normalization of the depressed baroreceptor reflex control of heart rate, even with the persistence of hypertension in losartan-treated animals (Am J Physiol. 1995;269:H812-H818). In the present study we analyzed the effects of angiotensin II blockade on afferent aortic nerve activity of CH and sham-operated groups treated chronically with vehicle or losartan (10 mg/kg per day p.o.). CH was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 8 days (4 control and 4 experimental days). Aortic pressure (conscious rats) and aortic nerve activity simultaneous to pressure (anesthetized rats) were recorded on the fourth day of the experimental period. Losartan-treated rats showed reduced tail pressure (104+/-3 versus 117+/-3 mm Hg in the vehicle group). In both groups, aortic coarctation caused a significant increase in pressure (25% and 28%, respectively) and a depression of the aortic nerve activity/pressure relationship when compared with sham-operated coarcted animals. In the physiological range of pressure changes, the depression was significantly smaller after losartan treatment (3.30+/-0.33 versus 2.18+/-0.37%/mm Hg in the losartan- and vehicle-treated CH groups, respectively, versus 5.05+/-0.33%/mm Hg in the sham-operated vehicle-treated group). Angiotensin type 1 (AT1) receptor blockade was also accompanied by reduced variability of the afferent discharge. The data suggested that apart from its pressure effect, angiotensin II acts at AT1 receptors to decrease the sensitivity of aortic afferents during physiological (+/-10 mm Hg) increases and decreases in pressure. Thus, angiotensin II may contribute to reductions of baroreceptor gain in chronic hypertension.