In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 6 ( 1999-06), p. 1420-1424
Abstract:
Abstract —Previous studies in dogs have shown additive or even synergistic effects of combined angiotensin-converting enzyme inhibition and either nonselective endothelin subtype A/B (ET A/B ) or selective endothelin subtype A (ET A ) receptor blockade on renal vascular resistance and mean arterial blood pressure. A possible mechanism underlying this interaction may be a stimulation of the renin-angiotensin system during endothelin (ET) receptor blockade. We therefore investigated whether plasma renin activity and renin release are regulated by the ET A receptor. Experiments were made in conscious, chronically instrumented dogs receiving either saline or the selective ET A receptor antagonist LU 135252 (10 mg/kg IV). Eighty to 100 minutes after the administration of LU 135252 (n=5), heart rate (99±7 versus 81±6 bpm; P 〈 0.05) and renal blood flow (327±40 versus 278±36 mL/min; P 〈 0.05) were increased significantly, whereas mean arterial blood pressure tended to be lower (93±5 versus 105±7 mm Hg). These changes were associated with a 2-fold increase in plasma renin activity (0.74±0.12 versus 0.37±0.10 ng angiotensin I per milliliter per hour; P 〈 0.05). Measurements of renin release at various renal perfusion pressures (n=5) with the use of a vascular occluder implanted around the left renal artery revealed that ET A receptor blockade did not alter renin release at resting renal perfusion pressure (78±25 versus 71±39 U/min) but strongly enhanced the sensitivity of pressure-dependent renin release 〈 80 mm Hg ≈2.2-fold. In conclusion, selective ET A receptor blockade is associated with a stimulation of the circulating renin-angiotensin system, which results from both a sensitization of pressure-dependent renin release and a larger proportion of blood pressure values falling into the low pressure range, where renin release is stimulated. These find-ings strengthen the view that ET and the renin-angiotensin system closely interact to regulate vascular resistance and provide a physiological basis for synergistic hypotensive effects of a combined blockade of both pressor systems.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.33.6.1420
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1999
detail.hit.zdb_id:
2094210-2
