Increased cardiac work provides a link between systemic hypertension and heart failure

Abstract

The spontaneously hypertensive rat (SHR) is an established model of human hypertensive heart disease transitioning into heart failure. The study of the progression to heart failure in these animals has been limited by the lack of longitudinal data. We used MRI to quantify left ventricular mass, volume, and cardiac work in SHRs at age 3 to 21 month and compared these indices to data from Wistar‐Kyoto (WKY) controls. SHR had lower ejection fraction compared with WKY at all ages, but there was no difference in cardiac output at any age. At 21 month the SHR had significantly elevated stroke work (51 ± 3 mL.mmHg SHR vs. 24 ± 2 mL.mmHg WKY; n = 8, 4; P < 0.001) and cardiac minute work (14.2 ± 1.2 L.mmHg/min SHR vs. 6.2 ± 0.8 L.mmHg/min WKY; n = 8, 4; P < 0.001) compared to control, in addition to significantly larger left ventricular mass to body mass ratio (3.61 ± 0.15 mg/g SHR vs. 2.11 ± 0.008 mg/g WKY; n = 8, 6; P < 0.001). SHRs showed impaired systolic function, but developed hypertrophy to compensate and successfully maintained cardiac output. However, this was associated with an increase in cardiac work at age 21 month, which has previously demonstrated fibrosis and cell death. The interplay between these factors may be the mechanism for progression to failure in this animal model.

Neurotransmitter Switching Coupled to β-Adrenergic Signaling in Sympathetic Neurons in Prehypertensive States

“…To establish whether increased βAR signaling in pre-SHR results from increases in βAR expression, we measured levels of β 1 AR and β 2 AR mRNA via qRT-PCR and RNAseq and quantified protein levels using sandwich ELISAs. Surprisingly, we observed that βAR transcripts and protein expression are reduced in pre-SHR stellates, as well as in aged SHR with established hypertension, 6 , 29 – 31 , 33 , 35 , 36 , 42 compared with age-matched Wistar neurons, in a similar manner to that reported in the myocardium. 64 , 65 We also report that in healthy ganglia, β 1 AR expression decreases with age, much like in the heart (Figure 1 ).…”

“…At 16 weeks, it is well-established that SHR display hypertension and sympathetic hyperactivity. 6 , 29 – 31 , 33 , 35 , 36 , 42 Using quasi-mapping RNAseq 43 and quantitative real-time (qRT)-polymerase chain reaction (PCR), we identified the presence of β 1 AR ( Adrb1 ) and β 2 AR ( Adrb2 ) mRNA transcripts, in addition to α 2A AR ( Adra2a ) and tyrosine hydroxylase ( Th ) mRNA transcripts, markers of presynaptic sympathetic neurons, respectively (Figure 1 A; Figure S1). We selected the α 2A AR isoform as an indicator of presynaptic neuronal phenotype based on reports that the α 2A AR primarily regulates presynaptic sympathetic activity.…”

“…The SHR strain displays normal blood pressure at 4 weeks of age, where increases in arterial blood pressure develop progressively from 5 to 6 weeks of age. 29 – 36 In this study, we used the Wistar rat strain as the normotensive control, given that Wistar rats are the progenitor strain from which the Wistar Kyoto was bred and the 2 strains display similar hemodynamic profiles at all ages. 31 , 32 , 36 – 41 In addition, neither strain display a sympathetic Ca 2+ phenotype (Figure S1A), making the Wistar a suitable control in this study.…”

Efeitos hemodinâmicos, inflamatórios e histológicos após a exposição à exaustão do combustível diesel em modelo experimental de hipertensão arterial

“…2014). A hipertrofia concêntrica e disfunção diastólica são tradicionalmente associadas a um pequeno volume diastólico, enquanto o mesmo está associado a um ventrículo dilatado e disfunção (Wilson A. J. et al 2017). A insuficiência cardíaca é uma condição em que o coração é incapaz de bombear sangue suficiente para atender às demandas metabólicas do corpo.…”

“…A insuficiência cardíaca é uma condição em que o coração é incapaz de bombear sangue suficiente para atender às demandas metabólicas do corpo. A prevalência mundial de insuficiência atingem mais de 23 milhões de pessoas (Roger 2013 (Wilson A. J. et al 2017).…”