Effects of Testosterone Deficiency and Angiotensin II–Induced Hypertension on the Biomechanics of Intramural Coronary Arteries

Abstract

Background Andropause and hypertension also increase the risk of coronary artery damage. Aim To investigate the effect of testosterone deficiency and hypertension on intramural coronary vessels. Methods 4 groups of 8-week-old Sprague-Dawley rats were studied: control male (Co, n=10), orchidectomized male (OCT, n=13), angiotensin (AII) hypertensive male (AII, n=10), and AII hypertensive and OCT (AII + OCT, n=8). Surgical orchidectomy was performed, and an osmotic minipump was inserted for chronic angiotensin II infusion (100 ng/min/kg). After 4 weeks, spontaneous tone and biomechanical properties of the intramural coronary resistance artery were investigated in vitro, by pressure microarteriography. Outcomes Morphology and biomechanics of the intramural coronaries were evaluated: the outer diameter, wall thickness–to–lumen diameter ratio, and tangential wall stress in the contracted and relaxed states. Results The outer diameter was reduced in OCT and AII + OCT groups (on 50 mmHg 315 ± 20 Co; 237 ± 21 OCT; 291 ± 16 AII, and 166 ± 12 μm AII + OCT). The increased wall thickness–to–lumen diameter ratio resulted in lower tangential wall stress in AII + OCT rats (on 50 mmHg 19 ± 2 Co; 24 ± OCT; 26 ± 5 AII, and 9 ± 1 kPa AII + OCT). Spontaneous tone was increased in the hypertensive rats (AII and AII + OCT groups) (on 50 mmHg 7.7 ± 1.8 Co; 6.1 ± 1.4 OCT; 14.5 ± 3.0 AII, and 17.4 ± 4.1 % AII + OCT). Clinical Implications Andropause alone can be considered as a cardiovascular risk factor that will further exacerbate vascular damage in hypertension. Strengths & Limitations A limitation of our study is that it was performed on relatively young rats, and the conclusions might not apply to coronary remodelling in older animals with slower adaptation processes. Conclusions Testosterone deficiency and hypertension damage the mechanical adaptation of the vessel wall additively: double noxa caused inward eutrophic remodeling and increased tone.

Additive damage in the thromboxane related vasoconstriction and bradykinin relaxation of intramural coronary resistance arterioles in a rodent model of andropausal hypertension

“…We choose week 4 in our series to perform experiments as this corresponds with the early stages of hypertension. In our previous publication [ 37 ] this AII infusion increased both systolic and mean blood pressure values in compared to the Co rats. Hormone deficiency lead to decreases blood pressure in the group of hypertensive rats (AII + ORC) compared with the rats that did not undergo orchidectomy AII-infused animals.…”

“…Rats were anesthetized with Euthasol (by CEVA Santé Animale, Liboume, France). Hypertension was established via an Angiotensin (AII) modelas described previously [ 32 , 37 , 38 , 39 ]. An osmotic minipump (by Alzet, 2ML4, Durect Co, Cupertino, US) containing AII (Sigma-Aldrich Co, St. Louis, Missouri, US and Budapest, Hungary) was implanted subcutaneously.…”

“…The animals that received a treatment of AII (AII and AII + ORC) had osmotic minipumps surgically implanted under anesthesia (45 mg/kg intraperitoneal pentobarbital), subcutaneously into the region above the lumbar spine. The infusion rate of the AII infusion minipump was 100 ng/kg/min, which leads to chronic blood pressure elevation without any acute pressure effects in 2–3 weeks [ 37 , 38 , 39 ]. We choose this AII hypertension model to study coronary arteries alterations in the early hypertensive state.…”

“…There is significantly less data available regarding effects of a deficiency of testosterone combined with hypertension on resistence arteries [ 26 , 36 ]. The effects of testosterone-deficiency and hypertension together on the morphology and also on the biomechanical characteristics of resistance coronaries were first examined by our team [ 37 ]. In brief: as a result of hypertension, spontaneous tone increases first, even without remodeling of wall structure.…”

“…Testosterone deficiency alone results in inward hypotrophic remodeling, which persists in double noxa. Hypertensive stimulus with testosterone deficiency further reduces vessel diameter [ 37 ]. However, little is known about the functional adaptation of blood vessels affected by the double noxa [ 26 ].…”