1. Academic Validation
  2. sGC stimulation lowers elevated blood pressure in a new canine model of resistant hypertension

sGC stimulation lowers elevated blood pressure in a new canine model of resistant hypertension

  • Hypertens Res. 2021 Dec;44(12):1568-1577. doi: 10.1038/s41440-021-00748-5.
Julia Vogel 1 2 3 Philip Boehme 2 Susanne Homann 4 Mario Boehm 5 Katharina Andrea Schütt 6 Katharina Boden 1 2 Jakob Balitzki 1 7 Jörg Hüser 1 Wilfried Dinh 1 2 8 Hubert Truebel 1 2 Peter Sandner 1 7 Thomas Mondritzki 9 10
Affiliations

Affiliations

  • 1 Bayer AG, Wuppertal, Germany.
  • 2 University of Witten/Herdecke, Witten, Germany.
  • 3 University of Duisburg-Essen, Essen, Germany.
  • 4 Heinrich-Heine-University, Düsseldorf, Germany.
  • 5 Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University Giessen, German Center for Lung Research (DZL), Giessen, Germany.
  • 6 Department of Internal Medicine I, University Hospital RWTH Aachen, Aachen, Germany.
  • 7 Hannover Medical School, Hannover, Germany.
  • 8 Department of Cardiology, HELIOS University Clinic Wuppertal, Wuppertal, Germany.
  • 9 Bayer AG, Wuppertal, Germany. thomas.mondritzki@bayer.com.
  • 10 University of Witten/Herdecke, Witten, Germany. thomas.mondritzki@bayer.com.
Abstract

Therapy-resistant hypertension is a serious medical problem, causing end-organ damage, stroke, and heart failure if untreated. Since the standard of care fails in resistant hypertension patients, there is still a substantial unmet medical need for effective therapies. Active stimulation of soluble guanylyl cyclase via novel soluble guanylyl cyclase stimulators might provide an effective treatment option. To test this hypothesis, we established a new experimental dog model and investigated the effects of the soluble guanylyl cyclase-stimulator BAY 41-2272. In beagle dogs, a resistant hypertension phenotype was established by combining unilateral renal wrapping with the occlusion of the renal artery in the contralateral kidney. The most frequently used antihypertensive drugs were administered orally, either alone or in combination, and their acute effect on telemetric measured blood pressure was assessed and compared with that of BAY 41-2272. The chosen disease stimulus led to a moderate and stable increase in blood pressure. Even high doses of standard-of-care antihypertensives only slightly decreased blood pressure. In contrast, the administration of the soluble guanylyl cyclase stimulator BAY 41-2272 as standalone therapy led to a dose-dependent reduction in blood pressure (-14.1 ± 1.8 mmHg). Moreover, BAY 41-2272 could also further decrease blood pressure in addition to a triple combination of standard-of-care antihypertensives (-28.6 ± 13.2 mmHg). BAY 41-2272 was highly efficient as a standalone treatment in resistant hypertension but was also effective in addition to standard-of-care treatment. These data strongly suggest that soluble guanylyl cyclase stimulators might provide an effective pharmacologic therapy for patients with resistant hypertension.

Keywords

Animal model; BAY 41-2272; Hypertension; sGC stimulator.

Figures
Products