Pressure-flow relationships of the canine iliac periphery and systemic hemodynamics: Effects of sodiumnitroprusside and adenosine

It has been reported that sodiumnitroprusside (SNP) decreases mean systemic pressure and simultaneously increases pressure pulse amplification towards the iliac periphery (Kenner and van Zwieten 1982). This unexpected finding was suggested to be due to a decrease in iliac peripheral resistance but an increase in iliac differential resistance. In order to investigate this apparent contradiction, the iliac periphery was hemodynamically isolated from the rest of the circulation and perfused with the dog's own blood by means of a pump. Perfusion pressure (P) and flow (F), femoral venous pressure (P_v), systemic pressure (P_s) and cardiac output (CO) were measured. Steady state pressure-flow relations of the isolated bed were obtained during control and during various i.v. infusion rates of SNP and adenosine (ADS) and were found to be straight (meanr=0.99). Their slope (P/F) was defined as differential resistance (R_d). Peripheral resistance (R_p) of the iliac bed was defined as R_p=(P-P_v)/F, calculated at the flow value where perfusion pressure equalled the prevailing systemic pressure. Total peripheral resistance (TPR) was defined as TPR=P_s/CO. The changes of R_d, R_p, P_s, CO and TPR with respect to control show that during low SNP infusion rates R_d and R_p were both increased while TPR was decreased. During all infusion rates of SNP CO did not change while P_s decreased. During low infusion rates of adenosine CO increased while P_s, R_d and R_p did not change and TPR decreased. During high infusion rates of ADS CO decreased again, R_d, R_p and P_s decreased, and TPR remained constant but at a decreased level.It is concluded that: (1) the suggestion of Kenner and van Zwieten is not supported, since SNP (as well as ADS) affects iliac peripheral and iliac differential resistance in a similar way; (2) SNP (as well as ADS) affects iliac peripheral resistance and total peripheral resistance in a differentiated way, and even in an opposite way during low infusion rates of SNP; (3) it is this opposite effect that explains the paradoxical observations of Kenner and van Zwieten; (4) for comparable reductions of TPR, CO is better maintained during infusion of SNP, while P_s is better maintained during infusion of ADS.     

Serum and saliva levels of a trimethoprim-sulfamethopyrazine combination in man

Summary The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and a diuretic. After a 50 mg oral dose mean (± SD) peak plasma concentration of T was 1.13±0.29 µg/ml^–1 and occurred 0.79±0.40 h after the dose; mean peak plasma concentration of its sulphone metabolite (M) was 0.37±0.09 µg/ml^–1 at 1.92±1.32 h after the dose. Following peak plasma concentrations there was a monoexponential decline in T and M concentrations with half-lives of 2.78±0.77 h and 10.78±7.85 h respectively. There was a linear increase in plasma concentration of T and M during incremental dosing with 50–200 mg t. i. d. During in-patient administration of 600–900 mg T daily (n=6) there was no significant change in blood pressure, pulse rate or body weight. Out-patient administration of 900 mg T daily (n=4) was associated with a significant fall in mean systolic but not diastolic bp (lying –15/+1 mm Hg. standing –25/–8 mm Hg). A further fall was observed in 2 subjects receiving 1200 mg and 1500 mg daily. Supine pulse rate increased (mean ± SD) significantly from 55±5/min to 66±8/min following 900–1500 mg T in 4 out-patients. Severe nausea and other gastro-intestinal side-effects in all subjects receiving 600–900 mg daily eventually necessitated drug withdrawal. In its present from T is not recommended for the treatment of hypertension.     

Sex-specific endothelial dysfunction induced by high-cholesterol diet in rats: The role of protein tyrosine kinase and nitric oxide

Background and aimsAtherosclerosis is a chronic process playing a crucial role in the pathogenesis of cardiovascular disease. Sex-specific differences in the incidence of atherosclerosis indicate that estrogen has a protective effect on the cardiovascular disease. However, the role of sex on endothelium responses in animal models of high cholesterol (HC) diet-induced atherosclerosis has not been fully investigated. This study was aimed to investigate vascular responses in HC-fed rats.Methods and resultsMale and female Sprague rats (12-week-old) were treated with either a standard diet (n = 12 of each sex) or an HC enriched diet (n = 12 of each sex) containing 2% cholesterol for 24 weeks. HC treated animals (both sexes) showed increased levels of total cholesterol, LDL-cholesterol, triglyceride and blood pressure (BP) compared to control rats. While the BP of control rats (both sexes) was increased following aminoguanidine administration (AG, 100 mg/kg i.p.), it was not changed in HC animals (both sexes). The hypotensive effect of acetylcholine was significantly impaired in male HC-treated rats. In vitro experiments demonstrated that aortic rings from HC group (both sexes) had an increased contractile response to phenylephrine and a decreased vasodilatory response to acetylcholine. The vasorelaxant effect of acetylcholine in HC rats (only male) was improved by applying 10^?5 M genistein (tyrosine kinase inhibitor) or AG.ConclusionHC diet alters endothelium function through Nitric oxide (NO) and tyrosine kinase pathways in male rats.     

Urinary vasodilator and vasoconstrictor angiotensins during menstrual cycle, pregnancy, and lactation

Since normal human pregnancy is characterized by normotension in the face of an increased renin-angiotensin-aldosterone system (RAAS), we evaluated the temporal pattern of urinary excretion of a novel vasodilator within this system, angiotensin-(1–7) (Ang-[1–7]), during the menstrual cycle, pregnancy, and lactation. The urinary profiles of Ang I, Ang II, human chorionic gonadotropin, 17β-estradiol, and progesterone were also determined. During the menstrual cycle, urinary Ang-(1–7) and Ang II remained stable (mean cycle value: 94.6±11.3 and 11.4±1.1 pmol/g of creatinine, respectively) in nine females. In 10 normal pregnant women, urinary Ang-(1–7) and Ang II increased throughout gestation, averaging 1499.8±310 and 224.4±58 pmol/g of creatinine, respectively (p<0.05) at wk 35 and falling during lactation to 394.0±95 and 65.7±20 pmol/g of creatinine (p<0.05), respectively. The Ang-(1–7)/Ang II ratio was unchanged in the different reproductive periods. During the menstrual cycle, Ang II and Ang-(1–7) correlated with 17β-estradiol and progesterone using multivariate analysis (r=0.31, p<0.001) and r=0.28, p<0.02, respectively). During gestation, 17β-estradiol and progesterone correlated with urinary Ang-(1–7) (r=0.48, p<0.001 and r=0.47, p<0.001, respectively) and Ang II (r=0.24, p<0.03 and r=0.25, p<0.03, respectively); by multiple regression, only Ang-(1–7) correlated with both steroids (r=0.49, p<0.001). The progressive rise of Ang-(1–7) throughout gestation, probably modulated by estrogen and progesterone, suggests a physiologic counterregulation within the RAAS.     

Hydralazine-associated Amenorrhea in a Premenopausal Patient With Chronic Kidney Disease: A Case Report and Review of Literature

Purpose

Several antihypertensive medications have been associated with various forms of sexual dysfunction. We present a case report of a premenopausal patient with hydralazine-associated amenorrhea.

Improvement of Renal Function in Type 2 Diabetic Nephropathy

Background. Therapeutic failure in preventing renal disease progression in type 2 diabetic nephropathy (DN) is due to a failure in the early detection of DN by microalbuminuria and the inappropriate correction of renal hemodynamic maladjustment secondary to glomerular endothelial dysfunction. Methods. Thirty patients associated with normoalbuminuric type 2 DN were subject to the following studies: tubular function by means of fractional excretion of magnesium (FE Mg), vascular function by means of determining the circulating endothelial cell, VEGF, VEGF/TGF B ratio, and intrarenal hemodynamic studies. Results. FE Mg, circulating endothelial cells, and TGF B were abnormally elevated, and VEGF/TGF B ratio was decreased in these normoalbuminuric patients. The intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by a preferential constriction at the efferent arteriole and a reduction in peritubular capillary flow. Following treatment with vasodilators, a decrease in efferent arteriolar resistance and increase in peritubular capillary flow as well as glomerular clearance were observed. Conclusion. FE Mg appears to be a more sensitive marker than microalbuminuria for the early detection of DN. Increased endothelial cell injury is reflected by enhanced circulating endothelial cell loss in conjunction with the increased TGF B and the decreased ratio between VEGF and TGF B. This is further supported by the dysfunctioning glomerular endothelium, which is characterized by hemodynamic maladjustment and a reduction in the peritubular capillary flow. A correction of such hemodynamic maladjustment by multidrug vasodilators effectively improves renal perfusion and restores renal function in type 2 DN.     

Expresividad variable de una mutación fundadora en el gen EIF2AK4 en pacientes con enfermedad venooclusiva pulmonar hereditaria. Impacto en la supervivencia

Introduction and objectives

Hereditary pulmonary veno-occlusive disease (PVOD) has been associated with biallelic mutations in EIF2AK4 with the recent discovery of a founder mutation in Iberian Romani patients with familial PVOD. The aims of this study were phenotypical characterization and survival analysis of Iberian Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial genetic screening was conducted, as well as assessment of sociocultural determinants with a potential influence on disease course.

Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 ± 5 to 107 ± 3 mm Hg: mean ± SEM; P < 0.002) and diastolic blood pressure (from 85 ± 3 to 75 ± 2 mm Hg; P < 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 ± 2 to 27 ± 2 mm Hg (P < 0.005). The left ventricular filling pressure decreased from 24 ± 1 to 19 ± 1 mm Hg (P < 0.0001). A significant increase in cardiac index (from 2.33 ± 0.13 to 2.69 ± 0.15 l/min per m²; P < 0.001) and in stroke volume index (from 24 ± 2 to 28 ± 2 ml/beats per m²; P < 0.005) was registered. Systemic vascular resistance fell from 1742 ± 145 to 1308 ± 85 dynes/sec per cm⁻⁵ (P < 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 ± 1.6 to 5.1 ± 1.2 mm Hg; P < 0.0001), in mean pulmonary arterial pressure (from 32 ± 1 to 23 ± 1 mm Hg; P < 0.00001) and in left ventricular filling pressure (from 23 ± 1 to 16 ± 1 mm Hg; P < 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.