Sildenafil prevents right ventricular hypertrophy and improves heart rate variability in rats with pulmonary hypertension secondary to experimental diabetes

Clin Exp Hypertens. 2022 May 19;44(4):355-365. doi: 10.1080/10641963.2022.2050743. Epub 2022 Mar 20.

Abstract

Chronic treatment with sildenafil (SILD) is an effective protector on the development of cardiovascular complications of pulmonary hypertension (PH) and diabetes. However, to date, no studies have evaluated the effect of SILD on cardiopulmonary pathophysiology during PH secondary to type 1 diabetes.

Aim: The present study aimed to evaluate the beneficial effects of chronic SILD treatment on pulmonary arterial pressure, right ventricular hypertrophy (RVH) and cardiac autonomic dysfunction in rats with PH secondary to diabetes.

Metodology: Male Sprague Dawley rats were randomly distributed into the control group (saline), diabetic group (60 mg/kg with streptozotocin), SILD-treated control group (20 mg/kg) and SILD-treated diabetic group.

Results: After 8 weeks the type 1 diabetic animals presented PH, endothelial dysfunction of the pulmonary arteries, electrocardiographic alterations, RVH and overexpression of phosphodiesterase type 5 in the heart. In type 1 diabetic animals, SILD treatment prevented the development of PH, endothelial dysfunction and RVH. SILD treatment also prevented alterations in the corrected QT period and heart rate variability and prevented overexpression of phosphodiesterase type 5.

Conclusion: Our results indicate for the first time that SILD treatment prevents pulmonary arterial endothelial dysfunction, pulmonary hypertension, right ventricular hypertrophy and improves heart rate variability in type 1 diabetic rats.

Keywords: Sildenafil; cardiac autonomic neuropathy; diabetes mellitus; pulmonary hypertension; right ventricular hypertrophy.

MeSH terms

  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Type 1* / complications
  • Disease Models, Animal
  • Heart Rate
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / etiology
  • Hypertension, Pulmonary* / prevention & control
  • Hypertrophy, Right Ventricular / etiology
  • Hypertrophy, Right Ventricular / prevention & control
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sildenafil Citrate / pharmacology

Substances

  • Sildenafil Citrate
  • Cyclic Nucleotide Phosphodiesterases, Type 5