Age- and Hypertension-Related Changes in NOS/NO/sGC-Derived Vasoactive Control of Rat Thoracic Aortae

Abstract

This study was aimed at examining the role of the NOS/NO/sGC signaling pathway in the vasoactive control of the thoracic aorta (TA) from the early to late ontogenetic stages (7 weeks, 20 weeks, and 52 weeks old) of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Systolic blood pressure (SBP) and heart rate (HR) were significantly increased in SHRs compared to age-matched WKYs, which was associated with left heart ventricle hypertrophy in all age groups of rats. The plasma urea level was increased in 20-week-old and 52-week-old SHRs compared with WKYs without increasing creatinine and uric acid. The total cholesterol levels were lower in 20-week-old and 52-week-old SHRs than in WKYs, but triglycerides were higher in 7-week-old SHRs. The fructosamine level was increased in 52-week-old SHRs compared with age-matched WKYs and unchanged in other age groups. Superoxide production was increased only in 7-week-old SHRs compared to age-matched WKYs. The endothelium-dependent relaxation (EDR) of the TA deteriorated in both rat strains during aging; however, endothelial dysfunction already occurred in 20-week-old SHRs and was even more enhanced in 52-week-old rats. Our results also demonstrated increased activity of NOS in 52-week-old WKYs. Moreover, 7-week-old and 52-week-old WKY rats displayed an enhanced residual EDR after L-NMMA (NOS inhibitor) incubation compared with 20-week-old rats. Our results showed that in 7-week-old SHRs, the residual EDR after L-NMMA incubation was increased compared to that in other age groups. The activity of NOS in the TA was comparable in 7-week-old and 20-week-old SHRs, but it was reduced in 52-week-old SHRs compared to younger SHRs and 52-week-old WKYs. Thus, it seems that, in contrast to SHRs, the NOS/NO system in WKYs is probably able to respond to age-related pathologies to maintain endothelial functions and thus optimal BP levels even in later periods of life.

The Phthalic Selenoanhydride Decreases Rat Blood Pressure and Tension of Isolated Mesenteric, Femoral and Renal Arteries

“…However, R-Se compound at higher concentration evoked only mild vasorelaxant effect in thoracic aorta. Since the relaxation in thoracic aorta is mainly NO-mediated [74], these results are aligned with the suggestion that R-Se could relax the vessel wall by a mechanism excluding NO derived from the endothelium. There are other endothelium-derived relaxing factors (EDRFs), such as prostacyclin or endothelium-derived hyperpolarizing factors (EDHFs), which could participate in the R-Se related relaxation.…”

Ca2+-Dependent Cl− Channels in Vascular Tone Regulation during Aging

“…Aging impairs the NOS activity [3]. A recent experimental study revealed that in SHRs, aging leads to deterioration of the NOS system; conversely, the NOS system in WKY rats maintains its endothelial functions, leading to maintenance of optimal blood pressure levels even in later periods of life [4]. It is hypothesized that increased NOS activity in rostral ventrolateral medulla (RVLM) causes inhibition of renal sympathetic nerve activity (RSNA), which further reduces NOS activity in the kidney [57].…”

“…In central and peripheral arteries, age-dependent changes are associated with a progressive decline in vascular responses to constrictors [2]. Several other mechanisms involved in age-dependent vascular changes have been described, such as impaired nitric oxide synthase (NOS) activity [3,4], activation of Rho kinase [2,5], alterations in sympathetic nerve activity (SNA) [6,7], adrenergic regulation [8,9], increased vascular endothelin levels [10], alteration in prostaglandins production or release [11,12], and sexual blood pressure dimorphism [13].…”

Aging in Normotensive and Spontaneously Hypertensive Rats: Focus on Erythrocyte Properties

“…All rats were born in an accredited establishment at the Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, to keep an equal environmental background. This study represents part of a more complex experiment with already published details of the experimental protocol and some procedures previously [20,21]. Briefly, animals were housed from 2 to 4 per cage at constant conditions, i.e., temperature (22-24 • C) and humidity (45-60%), 12 h light-dark cycle (light phase from 06:00 to 18:00) and freely accessible standard laboratory rat diet and drinking water.…”

“…According to age (7 weeks or young juvenile, 20 weeks or young adult and 52 weeks or older rats) and strain (WKY or SHR), the rats were divided into the following six groups: WKY-7, WKY-20, WKY-52 and SHR-7, SHR-20, SHR-52 (n = 5-12). General biometric and cardiovascular parameters were monitored: body weight (BW), heart left ventricle weight (LVW), heart rate (HR) and systolic blood pressure (BP) as described previously [20,21]. Trunk blood was collected in heparinized test tubes, while a portion of whole blood (10 µL) was taken to evaluate NO production by RBCs.…”