1.Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations.
Blázquez-Medela AM1, García-Sánchez O, Quirós Y, Blanco-Gozalo V, Prieto-García L, Sancho-Martínez SM, Romero M, Duarte JM, López-Hernández FJ, López-Novoa JM, Martínez-Salgado C. Medicine (Baltimore). 2015 Oct;94(41):e1617. doi: 10.1097/MD.0000000000001617.
Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys.We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage.Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments.The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats.
2.Inhibition of soluble epoxide hydrolase counteracts the development of renal dysfunction and progression of congestive heart failure in Ren-2 transgenic hypertensive rats with aorto-caval fistula.
Červenka L1,2, Melenovský V3, Husková Z1, Škaroupková P1, Nishiyama A4, Sadowski J5. Clin Exp Pharmacol Physiol. 2015 Jul;42(7):795-807. doi: 10.1111/1440-1681.12419.
The detailed mechanisms determining the course of congestive heart failure (CHF) in hypertensive subjects with associated renal dysfunction remain unclear. In Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension, CHF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). In these rats we investigated the putative pathophysiological contribution of epoxyeicosatrienoic acids (EETs) and compared it with the role of the renin-angiotensin system (RAS). We found that untreated ACF TGR exhibited marked intrarenal and myocardial deficiency of EETs and impairment of renal function. Chronic treatment of these rats with cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/L in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs, markedly improved survival rate, and increased renal blood flow, glomerular filtration rate and fractional sodium excretion, without altering RAS activity.
3.PTPRD gene associated with blood pressure response to atenolol and resistant hypertension.
Gong Y1, McDonough CW, Beitelshees AL, El Rouby N, Hiltunen TP, O'Connell JR, Padmanabhan S, Langaee TY, Hall K, Schmidt SO, Curry RW Jr, Gums JG, Donner KM, Kontula KK, Bailey KR, Boerwinkle E, Takahashi A, Tanaka T, Kubo M, Chapman AB, Turner ST, Pepine CJ, Cooper-DeHoff RM, Johnson JA. J Hypertens. 2015 Nov;33(11):2278-85. doi: 10.1097/HJH.0000000000000714.
OBJECTIVE: The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-blocker atenolol.
4.Inhibition of soluble epoxide hydrolase does not improve the course of congestive heart failure and the development of renal dysfunction in rats with volume overload induced by aorto-caval fistula.
Červenka L1, Melenovský V, Husková Z, Sporková A, Bürgelová M, Škaroupková P, Hwang SH, Hammock BD, Imig JD, Sadowski J. Physiol Res. 2015 Dec 29;64(6):857-73. Epub 2015 Jun 5.
The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/l in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance.
