Cardiac and pulmonary arterial remodeling after sinoaortic denervation in normotensive rats

Abstract

Blood pressure variability (BPV) and baroreflex dysfunction may contribute to end-organ damage process. We investigated the effects of baroreceptor deficit (10 weeks after sinoaortic denervation - SAD) on hemodynamic alterations, cardiac and pulmonary remodeling. Cardiac function and morphology of male Wistar intact rats (C) and SAD rats (SAD) (n=8/group) were assessed by echocardiography and collagen quantification. BP was directly recorded. Ventricular hypertrophy was quantified by the ratio of left ventricular weight (LVW) and right ventricular weight (RVW) to body weight (BW). BPV was quantified in the time and frequency domains. The atrial natriuretic peptide (ANP), alpha-skeletal actin (α-skelectal), collagen type I and type III genes mRNA expression were evaluated by RT-PCR. SAD did not change BP, but increased BPV (11±0.49 vs. 5±0.3 mmHg). As expected, baroreflex was reduced in SAD. Pulmonary artery acceleration time was reduced in SAD. In addition, SAD impaired diastolic function in both LV (6.8±0.26 vs. 5.02±0.21 mmHg) and RV (5.1±0.21 vs. 4.2±0.12 mmHg). SAD increased LVW/BW in 9% and RVW/BW in 20%, and augmented total collagen (3.8-fold in LV, 2.7-fold in RV, and 3.35-fold in pulmonary artery). Also, SAD increased type I (~6-fold) and III (~5-fold) collagen gene expression. Denervation increased ANP expression in LV (75%), in RV (74%) and increased α-skelectal expression in LV (300%) and in RV (546%). Baroreflex function impairment by SAD, despite not changing BP, induced important adjustments in cardiac structure and pulmonary hypertension. These changes may indicate that isolated baroreflex dysfunction can modulate target tissue damage.

Arterial pressure and cerebral blood flow variability: friend or foe? A review

“…The mechanical cardiac changes are typified by enhanced cardiac wall thickness and increased total myocardial wall area, and relative reduction in elastin (Su and Miao, 2001). There is also evidence that increased BPV induced by SAD increases cardiac expression of type I and III collagen, and atrial natriuretic peptide (Flues et al, 2012). These findings suggest that the hypertrophic cardiac changes in SAD are the consequence of collagen accumulation in addition to smooth muscle proliferation.…”

Порівняння Впливу Фіксованої Комбінації Периндоприл/Амлодипін На Ураження Органів-Мішеней У Пацієнтів З Артеріальною Гіпертензією З ішемічною Хворобою Серця Та Без Неї (Результати Дослідження EPHES)

“…Це відбувається за рахунок збільшення вмісту колагену, зменшення вмісту еластину, стимуляції росту гладком'язових клітин, виникнення некрозу кардіоміоцитів, моно-нуклеарної інфільтрації, звуження просвіту коро-нарних судин. Посилення гіпертрофії кардіоміоцитів відбувається частково й за рахунок збільшення наван-таження на фоні зменшення еластичності аорти [15,31,53]. Окрім того, варіабельність АТ асоціюється з більшим гломерулярним ураженням [31].…”

Blood Pressure Variability: Prognostic Value and Therapeutic Implications

“…Vascular hypertrophy induced by SAD is characterized by an increase in wall thickness, wall area, and wall thickness to internal diameter ratio with raise in the relative area of collagen and a decline in the relative area of elastin [21]. Therefore, aortic hypertrophy in SAD rats is partially due to collagen accumulation and smooth muscle cell growth [22].…”

“…In comparison with sham operated rats, SAD induces pulmonary hypertension, ventricular hypertrophy, and impairment of diastolic function in both left and right ventricle. In addition, increase of BPV induced by SAD increases cardiac expression of type I and III collagen, atrial natriuretic peptide, and -skeletal [22].…”