“
“Aldosterone, a specific mineralocorticoid receptor (MR) agonist

and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin II type 1 receptor antagonists (ARBs). However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “”aldosterone Doramapimod chemical structure breakthrough”" effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS) inhibitors) gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+ channel blockers (CCBs) have inhibitory actions on aldosterone production in in vitro and in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism

of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.”
“Objective-To evaluate deafness in American Paint Horses by phenotype, clinical findings, brainstem selleckchem auditory-evoked responses (BAERs), and endothelin B receptor (EDNBR) genotype.

Design-Case series and case-control studies.

Animals-14 deaf American Paint Sotrastaurin cell line Horses, 20 suspected-deaf American Paint Horses, and 13 nondeaf American Paint Horses and Pintos.

Procedures-Horses were categorized on the basis of coat color

pattern and eye color. Testing for the EDNBR gene mutation (associated with overo lethal white foal syndrome) and BAERs was performed. Additional clinical findings were obtained from medical records.

Results-All 14 deaf horses had loss of all BAER waveforms consistent with complete deafness. Most horses had the splashed white or splashed white-frame blend coat pattern. Other patterns included frame overo and tovero. All of the deaf horses had extensive head and limb white markings, although the amount of white on the neck and trunk varied widely. All horses had at least 1 partially heterochromic iris, and most had 2 blue eyes. Ninety-one percent (31/34) of deaf and suspected-deaf horses had the EDNBR gene mutation. Deaf and suspected-deaf horses were used successfully for various performance events. All nondeaf horses had unremarkable BAER results.