Abstract 641: Renal Denervation does not Lower Blood Pressure in Spontaneously Hypertensive Rats Treated with a Beta-1 Adrenergic Receptor Antagonist.
We have used the SHR as an animal model to understand how renal denervation (RDN) lowers blood pressure. In order to determine how concomitant antihypertensive drug therapy could affect the blood pressure response to RDN, we performed RDN both before and after chronic (several days) treatment via the drinking water with the selective alpha-1 adrenergic antagonist prazosin and the selective beta-1 adrenergic antagonist atenolol. In the presence of prazosin treatment, RDN (n=7) significantly (p<0.05) lowered mean arterial pressure (MAP) compared to sham operated (SO; n=6) SHR (Δ=–4.0±1.7mmHg in RDN-SHR vs +1.5±1.3 in SO-SHR). Subsequent addition of atenolol during prazosin treatment reduced MAP significantly in both groups, but MAP in SO-SHR fell to the same level as in RDN-SHR, i.e. the antihypertensive effect of RDN was lost. After discontinuation of all drug treatment, the change in MAP from pre-treatment baseline was –7.7±3.5mmHg in RDN-SHR and +3.0±4.0mmHg in SO-SHR, p=0.06). To test whether the BP response to RDN would be lost during blockade of beta-1 adrenergic receptors alone, we performed RDN in SHR (n=5) pre-treated with atenolol. Atenolol alone significantly reduced MAP (Δ=-20.7±2.5mmHg). Steady-state MAP was not further reduced by RDN (Δ=+2.1±0.9mmHg). When atenolol was withdrawn MAP rose but remained reduced from baseline (Δ= -9.5±0.9mmHg). This magnitude of BP reduction is comparable to what we have previously observed after RDN in untreated SHR. In summary, in SHR RDN does not lower BP in the presence of an effective antihypertensive dose of a beta-1 antagonist. This indicates that RDN is reducing BP in SHR by interrupting a mechanism also affected by beta-1 adrenergic receptor signaling. Although further investigation is necessary, the data suggest that possibility that patients on clinically effective antihypertensive doses of beta-blockers may not exhibit a good response to RDN.
Author Disclosures: J. Phelps: None. G. Fink: None.
- © 2014 by American Heart Association, Inc.