Differential contribution of endothelium-derived relaxing factors to vascular reactivity in conduit and resistance arteries from normotensive and hypertensive rats

Abstract

The endothelium contributes to the maintenance of vasodilator tone by releasing nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). In hypertension, endothelium-dependent relaxation is attenuated (a phenomenon referred to as endothelial dysfunction) and contributes to the increased peripheral resistance. However, which vasodilator among NO, PGI2, and EDHF is impaired in hypertension remains largely unknown. The present study was designed to study the exact contribution of NO, PGI2, and EDHF to vascular reactivity in conduit and resistance artery, under physiological and pathological conditions. The aorta and the second-order mesenteric artery from spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were used to measure the vasorelaxation with myograph technology, in the presence or absence of different inhibitors. The results showed that the endothelium-dependent vasodilatation in the conduit artery was mediated mainly by NO, whereas the resistant artery by NO, PGI2, and EDHF together. In hypertension, both NO-mediated relaxation in the conduit artery and NO-, PGI2-, and EDHF-mediated dilation in the resistant artery were markedly impaired. Furthermore, the endothelium-dependent and the endothelium-independent vasorelaxation in conduit artery was attenuated more pronouncedly than that in the resistant artery from hypertensive rats, suggesting that the conduit artery is more vulnerable to hypertensive condition. In conclusion, vasodilators including NO, PGI2, and EDHF contribute distinctively to endothelium-dependent relaxation in conduit and resistance artery under physiological and pathological conditions.

Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator of KCa2.x and KCa3.1 Channels

“…In hypertension, under reduced bioavailability of NO, and when vasorelaxation is impaired, EDH-type dilatation is an important compensatory dilator system [1]. This finding is in line with research using the experimental model of acquired angiotensin II-induced, deoxycorticosterone acetate-salt (DOCA-salt) hypertension in SHR and SHRSP [11,38,45,46] respectively.…”

Endothelial Dysfunction of Conduit Arteries in Patients with Repaired Coarctation of the Aorta

“…In resistance arteries, endothelium-dependent vasodilation is maintained not only by NO but also by prostacyclin and various endothelium-derived hyperpolarizing factors. 22) Furthermore, FMD is particularly sensitive to traditional risk factors (age, hypertension), whereas RH-PAT is more sensitive to metabolic risk factors, particularly BMI and DM. 23) Our results suggest that endothelial dysfunction in patients with r-CoA may occur more significantly in conduit arteries than in resistance arteries; however, it is difficult to confirm whether this difference is the cause or consequence.…”

REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine

“…Rats were anesthetized with isoflurane. Systolic blood pressure (SBP) was measured using tail-cuff plethysmography (TCP), as described previously[ 11 ]. TCP was performed using an automated approach (Alcott Biotech, Shanghai, China).…”

“…Thereafter, they were contracted using phenylephrine (PE, 1 μM) and relaxed using cumulative concentrations of acetylcholine (ACh) to investigate endothelium-dependent vasodilatation in the absence or presence of different inhibitors. The utilized inhibitors included L-NAME (a nitric oxide synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), and TEA (an inhibitor of endothelium-derived hyperpolarizing factor (EDHF))[ 11 , 13 ]. The dilation response to ACh was presented as the percentage of the contractile response induced by PE, and the maximal relaxation (Emax) was calculated for statistical analysis.…”