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Updated: Aug 9, 2026
In Vitro Model of Coronary Angiogenesis
Published on: March 10, 2020
In vivo visualization of subendocardial arteriolar response in renovascular hypertensive hearts
Toyotaka Yada1, Masami Goto, Osamu Hiramatsu
1Department of Medical Engineering and Systems Cardiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. yada@me.kawasaki-m.ac.jp
Insights
In renovascular hypertension, subendocardial arterioles show impaired endothelium-dependent vasodilation early on. Later stages reveal broader impairments in both endothelium-dependent and -independent responses, while ACE inhibitor effects remain stable.
Area of Science:
- Cardiovascular Physiology
- Renal Hypertension Research
- Vascular Pharmacology
Background:
- Renovascular hypertension (HT) significantly impacts vascular function, particularly in different myocardial layers.
- Understanding time-dependent changes in arteriolar responses is crucial for managing HT complications.
- Subendocardial (Endo) and subepicardial (Epi) arterioles may exhibit distinct alterations in hypertensive states.
Purpose of the Study:
- To investigate sequential changes in vascular reactivity of canine subendocardial and subepicardial arterioles during renovascular hypertension.
- To compare responses to endothelium-dependent and -independent vasodilators and ACE inhibitors at different stages of HT.
- To elucidate the differential impact of HT on vascular function in Endo versus Epi layers.
Main Methods:
- Utilized a charge-coupled device intravital microscope to assess arteriolar diameter (<120 microm) in canine models.
- Compared responses to acetylcholine (endothelium-dependent), papaverine (endothelium-independent), and cilazaprilat (ACE inhibitor).
- Evaluated vascular responses in normotensive (NT) dogs and dogs at 4 weeks (4wHT) and 12 weeks (12wHT) of renovascular hypertension.
Main Results:
- Acetylcholine-induced vasodilation was reduced in Endo arterioles at both 4wHT and 12wHT compared to NT.
- Epi arterioles showed reduced acetylcholine response only at 12wHT.
- Papaverine-induced vasodilation was impaired in Endo arterioles at 12wHT but not Epi.
- Vasodilation induced by cilazaprilat remained unchanged in both Endo and Epi arterioles at all time points.
- Endothelium-dependent responses were impaired earlier in Endo than Epi, and endothelium-independent responses were impaired later in Endo.
Conclusions:
- Early renovascular hypertension impairs endothelium-dependent vasodilation in subendocardial arterioles.
- Later stages of HT lead to impaired endothelium-dependent and -independent vasodilation in subendocardial arterioles and endothelium-dependent vasodilation in subepicardial arterioles.
- Vasodilatory responses to ACE inhibitors are preserved in both arteriolar beds throughout the hypertensive process.
Abstract:
Time-sequential responses to endothelium-dependent and -independent vasodilators and angiotensin-converting enzyme (ACE) inhibitors were studied in the subendocardial arterioles (Endo) of canine renovascular hypertension (HT) compared with subepicardial arterioles (Epi; both <120 microm) by charge-coupled device intravital microscope. Vascular responses to acetylcholine, papaverine, and cilazaprilat were compared between normotensive (NT) and HT dogs [4 wk and 12 wk of HT (4wHT and 12wHT)]. The acetylcholine-induced vasodilation of Endo in both 4wHT and 12wHT was smaller than that of NT (both P < 0.01 vs. 4wHT and 12wHT), and that of Epi was smaller than that of NT only in 12wHT (P < 0.05). The papaverine-induced vasodilation of Endo, but not Epi, was impaired only in 12wHT (both P < 0.01 vs. NT and 4wHT). Vasodilation by cilazaprilat remained unchanged at 4wHT and 12wHT in both Epi and Endo. In conclusion, at the early stage, the endothelium-dependent response of Endo was impaired, whereas at the later stage, the endothelium-dependent and -independent responses of Endo and the endothelium-dependent response of Epi were impaired. However, the vasodilatory responses to the ACE inhibitor were maintained in both Endo and Epi of HT.
