ECE2022 Poster Presentations Adrenal and Cardiovascular Endocrinology (87 abstracts)
Key role for vasopressin V2 receptors in hypertension development in Spontaneously Hypertensive Rats (SHRs)
Ignazio Verzicchio 1 , Alice Bongrani 1 , Stefano Tedeschi 1 , Gallia Graiani 2 , Stefania Cavazzini 3 , Jessica Zappa 1 , Barbara Palladini 1 , Elena Cremaschi 1 , Anna Calvi 1 , Pietro Coghi 1 , Vanni Vicini 1 , Valentina Cannone 1 , Riccardo Volpi 1,4 , Alberico Borghetti 1 & Aderville Cabassi 1
1Cardiorenal Research Unit - Clinica e Terapia Medica, Parma, Italy; 2Histology and Histopathology Unit and Molecular Biology Laboratory, Dental School, Parma, Italy; 3University of Parma, Laboratory of Industrial Toxicology, Department of Medicine and Surgery (DIMEC), Parma, Italy; 4Endocrinology and Andrology Unit, Clinica e Terapia Medica, Parma, Italy
Water and electrolyte balance regulation plays a key role in essential hypertension pathogenesis. Indeed, alterations in kidney ability to excrete sodium and water in relation to intake have been proposed as a basic process of hypertension development. Vasopressin (AVP) acts through V2 receptors on the basolateral membrane of collecting duct principal cells to trigger the phosphorylation of Aquaporin 2 (AQP2) which moves from the cytoplasm to the apical membrane, making the cell water-permeable and resulting in water reabsorption. In Spontaneously Hypertensive Rats (SHRs), the alterations in water and sodium balance, as well as in osmoregulation, were evaluated from the pre-hypertensive phase to the establishment of hypertension and further to hypertension-related organ damage; early AVP V1 and V2 receptor antagonism was also evaluated on blood pressure time-course. At 4-5 weeks of age, pre-hypertensive SHRs (n=58) showed reduced daily urine volume (P <0.01), increased urine osmolality (P <0.01) and a trend towards lower urine sodium excretion (P=0.079) compared to normotensive Wystar Kyoto rats (WKYs, n=46). Circulating levels of AVP were not different, while the urine AQP2/creatinine ratio (P <0.01), as well as the expression of Na+/K+ ATPase and betaine-amino-n-butyric acid transporter 1 (BGT1) in thick ascending limb in outer medulla (mTAL) were higher in pre-hypertensive SHRs than in WKYs. At 28–30 weeks of age, hypertensive SHRs with moderate renal failure displayed no difference in urine osmolality and renal BGT1 expression but showed similar urine AQP2/creatinine ratios with significantly higher circulating AVP levels (P <0.01). Treatment of SHRs (n=20) with the V1-antagonist OPC 21268 from 25 to 40 days of age slightly decreased blood pressure but after its withdrawal did not prevent the hypertension onset in adult age. In contrast, administration of tolvaptan, a V2 antagonist, delayed hypertension development by 4-5 weeks. In addition, tolvaptan-treated rats showed a significantly increased urine volume (P <0.01), as well as a decrease in urine osmolality (P <0.01) and urine AQP2/creatinine ratio (P <0.01) compared to both untreated (n=8) and anti-V1-treated (n=12) SHRs. Thus, according to our results, increased plasma levels of AVP seem to play a key role in hypertension development in SHRs through the activation of V2 receptors in the principal cells of the collecting duct, suggesting that alterations in water balance, even before sodium balance perturbations, represent a cardinal element in the pathogenesis of high blood pressure in this experimental model of hypertension.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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