Chronic Blockade of Brain Endothelin Receptor Type-A (ETA) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats

Abstract

Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ETA) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ETA blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein) in the right OB of hypertensive animals. However, ETA blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ETA are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

Differences in the response to periarterial nerve stimulation or exogenous noradrenaline infusion in the mesenteric vascular bed with the intestinal tract harvested from commonly used rat models of hypertension

“…The increased sympathetic tone found in DOCA-salt rats may be mediated by renal and central sympathetic mechanisms. 27,28 In the present study, the isolated mesenteric vascular bed without the kidney was used; therefore, data from the DOCA-salt group aligned with the results of previous studies. We implied that the elevation in the systemic blood pressure found in DOCA-salt rats is due to hypervolaemia and subsequent increased sympathetic tone.…”

“…Research suggests that the increase in sympathetic nerve excitation and the increased responsiveness of the vascular α 1 adrenergic receptor were associated with vascular constriction in the aorta or veins in DOCA‐salt rats. The increased sympathetic tone found in DOCA‐salt rats may be mediated by renal and central sympathetic mechanisms . In the present study, the isolated mesenteric vascular bed without the kidney was used; therefore, data from the DOCA‐salt group aligned with the results of previous studies.…”

Treatment with NaHS reduces systolic blood pressure and ameliorates oxidative stress in DOCA-Salt hypertensive rats

“…Thus, the hypothesis of this study was that in vivo treatment with NaHS in a chronic model of hypertension may cause reduction of systolic blood pressure. To test this hypothesis, a well-established model of chronic hypertension, DOCA-Salt nephrectomy model, [5,19,36,37] was applied and the results showed that the model caused a significant and persistent elevation of systolic blood pressure. In addition, NaHS was given as an H 2 S donor [38] to hypertensive rats.…”

“…Similarly, the pathogenesis of hypertension involves multiple dysregulations of the controlling mechanisms. Overactivation of the sympathetic nervous system, [3] oversecretion of vasoconstrictor hormones and peptides such as angiotensin II and endothelin [4,5], impairment of renal excretory functions [6] in addition to endothelial dysfunction [7,8] represent major pathways implicated in the development of hypertension. Moreover, increased oxidative stress, a hallmark of hypertension, [9] was found to contribute in the development of the previously mentioned pathophysiologic conditions.…”

Deneysel Hipertansiyon Modelinde Farklı DOCA-tuz Uygulama Sürelerinin Kan Basıncı ve Damar Cevapları Üzerine Etkisi

“…Hayvanlara sürekli olarak tuzlu içme suyu verilmiştir. DOCA enjeksiyonu ise haftada iki gün uygulanmıştır 14,15 .…”