Janusz Skrzypecki

Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats.

BACKGROUND Recent evidence suggests that an elevated plasma trimethylamine N-oxide (TMAO) level is associated with an increased risk of adverse cardiovascular events in humans; however, the mechanism is not clear. The aims of this study were to establish the plasma TMAO level in rats and to evaluate the effect of TMAO on arterial blood pressure (BP) and the hemodynamic effects of angiotensin II (Ang II). METHODS Twelve-week-old, Sprague-Dawley rats were implanted with telemetric transmitters, and continuous recordings of heart rate, systolic BP (SBP), and diastolic BP (DBP) were made for 7 days before and 14 days during osmotic minipump-driven subcutaneous infusion of saline (controls), TMAO, low-dose Ang II, or Ang II + TMAO. Plasma TMAO concentration was evaluated using liquid chromatography coupled with triple-quadrupole mass spectrometry. RESULTS The plasma TMAO concentration in controls was 0.57 μmol/L, whereas in TMAO-infused rats it was 58 μmol/L. Neither saline nor TMAO infusion affected SBP and DBP. Infusion of Ang II significantly increased SBP and DBP for the first 5 days of infusion only. In contrast, infusion of Ang II + TMAO produced a hypertensive response that lasted until the end of the experiment. TMAO infusions did not affect body weight and motor activity. CONCLUSIONS We showed that physiological plasma TMAO concentration in rats was approximately 10 times lower than that reported in humans. Furthermore, the new finding of the study is that TMAO does not affect BP in normotensive animals. However, it prolongs the hypertensive effect of Ang II.

Blood borne hormones in a cross-talk between peripheral and brain mechanisms regulating blood pressure, the role of circumventricular organs

Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood-brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified. In the paper we review studies on hemodynamic effects of catecholamines, neuropeptide Y, angiotensin II, aldosterone, natriuretic peptides, endothelins, histamine and bradykinin in the context of their role in a cross-talk between peripheral and brain mechanisms involved in the regulation of arterial blood pressure.

Drug Resistant Hypertension - No SIMPLE Way Out

Hypertension poses growing challenge for health policy-makers and doctors worldwide. Recently published results of Symplicity-III trial (HTN-3), the first blinded, randomized, multicenter study on the efficacy of renal denervation for the treatment of resistant hypertension did not show a significant reduction of BP in patients with resistant hypertension 6 months after renal-artery denervation, as compared with controls. In this paper we review clinical and experimental studies on renal denervation. In order to identify causes of inconsistent results in renal denervation studies we look at basic science support for renal denervation and at designs of clinical trials.

The effect of simvastatin and pravastatin on arterial blood pressure, baroreflex, vasoconstrictor, and hypertensive effects of angiotensin II in Sprague–Dawley rats

Research suggests that statins affect the regulation of arterial blood pressure (BP), however, the mechanisms remain obscure. We maintained male, 12-week-old, Sprague-Dawley rats on tap water (controls) or water containing simvastatin or pravastatin for 4 weeks. Subsequently, we measured mean arterial blood pressure and heart rate at baseline and after intravenous infusion of either saline or angiotensin II (Ang II). Additionally, we tested baroreflex function and the effect of statins on vasoconstrictor response to Ang II on isolated femoral artery branches. Controls and simvastatin and pravastatin groups showed a significant increase in mean arterial BP and heart rate in response to Ang II. The increase was significantly smaller in the simvastatin group than in controls and in the pravastatin group. In contrast, when pretreated with hexamethonium, a ganglionic blocker, simvastatin and pravastatin groups showed a similar hypertensive response to Ang II, which was smaller than in controls. Likewise, the Ang II-induced vasoconstrictor response of femoral artery branches was comparable between simvastatin and pravastatin groups and smaller than in controls. We found no effect of statins on the baroreflex. This study shows that simvastatin and pravastatin differ in their effects on the Ang II-dependent mechanisms controlling BP.

The Upright Body Position Increases Translaminar Pressure Gradient in Normotensive and Hypertensive Rats

ABSTRACT Aim: Several lines of evidence suggest that the pathogenesis of glaucoma may depend on an increased translaminar pressure gradient (TPG), the difference between intraocular and intracranial pressure (ICP), rather than on intraocular pressure (IOP) itself. It has also been suggested that high blood pressure might correlate with the incidence of glaucoma; however, the data are contradictory. Here, we studied the effect of arterial blood pressure and changes in body position on TPG in rats. Methods: Experiments were performed on anesthetized 15- to 16-week-old, male, spontaneously hypertensive rats (hypertensive rats, n = 10) and Wistar–Kyoto rats (normotensive rats, n = 10). Continuous recordings of intracranial and IOPs were performed before, during, and after changing the body position from horizontal to vertical. Results: At baseline, hypertensive rats had a significantly higher arterial blood pressure than normotensive rats, while intraocular and intracerebroventricular pressures and TPG did not differ between the groups. Changing the body position from horizontal to vertical produced a significant decrease in ICP, a nonsignificant decrease in IOP, and a significant increase in the TPG. There was no significant difference between normotensive and hypertensive rats in the pattern of changes in intraocular and intracerebroventricular pressures and TPG. Conclusions: Change in the body position from horizontal to vertical, but not hypertension, causes a significant increase in TPG in rats. If further studies confirm that TPG plays a role in the etiology of glaucoma, a vertical position and changes in the body position might be considered as debilitating factors.

Physician Review Portals Do Not Favor Highly Cited US Ophthalmologists

ABSTRACT Purpose: Physician review portals are becoming increasingly popular among patients and often serve as a primary advisory tool during the search for a doctor. However, it has not been established whether these platforms favor leaders of the field; i.e., physicians with high academic rank. Here, we assessed online ratings of US ophthalmologists, selected for their outstanding scientific performance. Methods: This cross-sectional, Internet-based study was performed in September 2016. First, we selected US ophthalmologists who published at least one manuscript or conference abstract that reached at least 100 citations from 2006 to 2016. Second, academic impact of preselected physicians, measured by overall number of citations or Hirsch index, was correlated with their ratings on two physician review portals: healthgrades.com and zocdoc.com. Results: We selected 105 ophthalmologists who met established criteria. A total of 78 were rated on healthgrades.com, but only two were rated on zocdoc.com. The average rating on healthgrades.com was 4.2 +/–0.9, similar to the previously reported US mean for a physician (∼4). The rating did not correlate with the number of citations or with Hirsh index. Conclusions: Highly cited ophthalmologist are not rated proportionately to their scientific achievements. Their reviews are positive, but do not stand out in comparison to other physicians. Additionally, we found that this group of ophthalmologists might be significantly underrepresented on particular review websites.

A common humoral background of intraocular and arterial blood pressure dysregulation

Abstract Background: It has been postulated that intraocular pressure, an important glaucoma risk factor, correlates positively with arterial blood pressure (blood pressure). However, results of experimental and clinical studies are often contradictory. It is hypothesized that, in some hypertensive patients, disturbances in intraocular pressure regulation may depend on biological effects of blood borne hormones underlying a particular type of hypertension, rather than on blood pressure level itself. Review: This review compares the effects of hormones on blood pressure and intraocular pressure, in order to identify a hormonal profile of hypertensive patients with an increased risk of intraocular pressure surge. The PUBMED database was searched to identify pre-clinical and clinical studies investigating the role of angiotensin II, vasopressin, adrenaline, noradrenaline, prostaglandins, and gaseous transmitters in the regulation of blood pressure and intraocular pressure. Results: Studies included in the review suggest that intraocular and blood pressures often follow a different pattern of response to the same hormone. For example, vasopressin increases blood pressure, but decreases intraocular pressure. In contrast, high level of nitric oxide decreases blood pressure, but increases intraocular pressure. Conclusions: Arterial hypertension is associated with altered levels of blood borne hormones. Contradicting results of studies on the relationship between arterial hypertension and intraocular pressure might be partially explained by diverse effects of hormones on arterial and intraocular pressures. Further studies are needed to evaluate if hormonal profiling may help to identify glaucoma-prone patients.

Patient-oriented mobile applications in ophthalmology: Mobile software in ophthalmology

Mobile solutions will improve patient care only if they are equally valued by physicians and their patients. Although mobile applications are gaining acceptance among ophthalmologists and optometrists, little is known about their adoption among patients. Therefore, this study was designed to analyse the market for patient‐oriented mobile applications in ophthalmology.

Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs

ABSTRACT The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.