A system of complementary genes in hybrids between Drosophila koepferae and D. buzzatii: a Markov chain model allows to make inferences about their number and relationships.

In backcrosses between D. koepferae and D. buzzatii, the disruption of a system of species-specific complementary factors brings about hybrid male inviability. This system consists of a lethal factor, hmi-1, linked to the X chromosome of D. koepferae, and several conspecific autosomal suppressors. However, hmi-1 hybrid males can also be rescued by factors present in some strains of D. buzzatii. The present work aims to estimate the number of hmi-1 suppressors in one of these strains by means of Markov chains. The obtained results allow discarding models with one or more chromosomes having independent suppressor effect. On the other hand, models having n chromosomes that interact in groups of r, being 1 < r < or = n, to produce rescue effect, provide good approximations to the observed results. The best fit to the data is obtained with four or five chromosomes with suppressor effect, interacting epistatically in groups of three to rescue the viability of hmi-1 males.

Effect of lacidipine and nifedipine GITS on platelet function in patients with essential hypertension.

With the aim of evaluating the effects on blood pressure, platelet function and insulin sensitivity of the dihydropiridines lacidipine and nifedipine GITS, a parallel double-blind study was carried out in a group of 20 patients with mild to moderate essential hypertension. They received a placebo for 4 weeks; then were divided at random into two groups of 10 patients each. Nifedipine GITS, 30 mg and lacidipine, 4 mg, were given during 16 weeks of active treatment. Blood pressure and heart rate were measured at the clinic in supine, sitting and standing positions, 24 +/- 1 h after the last dose. After the placebo and active phases were carried out, a platelet aggregation test was performed to determine platelet malondialdehyde production and a tolerance to 100 g of glucose by measuring glucaemia and plasma insulin. Both drugs reduced systolic and diastolic blood pressure at the same level, however there were observable differences in the rate of reduction. The nifedipine GITS reduced supine systolic blood pressure by 25 mm Hg in the first week, while the lacidipine did so by 11 mm Hg. At the end of the study period nifedipine reduced supine systolic blood pressure by 28 mm Hg and lacidipine by 20 mm Hg. Heart rate was increased slightly but significantly in the nifedipine GITS group only in the standing position. Both drugs reduced platelet aggregation ex vivo only marginally but they modified the malondialdehyde production, indicating an action on the arachidonic acid metabolic pathway.

Effects of amlodipine and enalapril on platelet function in patients with mild to moderate hypertension.

OBJECTIVE: The aim of this study was to compare the effect of amlodipine and enalapril on platelet aggregation, and platelet production of malondialdehyde in patients with mild to moderate arterial hypertension. PATIENTS AND METHODS: A parallel, double-blind, placebo-controlled study was carried out in 24 patients (2 groups of 12 patients each). Initially all patients received placebo for four weeks; then amlodipine, 5 mg daily or enalapril 20 mg daily taken once a day at 7 am. Dosage was doubled after 4 weeks when diastolic blood pressure was > 90 mmHg in sitting position, the treatment was continued for 12 weeks. At the end of placebo and active phases a platelet aggregation test, using adenosine diphosphate, collagen and adrenaline, and a platelet malondialdehyde production test, either in basal conditions (MDA-basal) and after the stimulation of arachidonic acid pathway by adding ethylmaleimide (MDA-activated) were carried out. RESULTS: Blood pressure was reduced by both agents, enalapril and amlodipine. Enalapril controlled 58.3% of hypertensive patients with an average dosage of 31.7 mg/daily. Amlodipine controlled 75% of patients with a dosage of 7.1 mg/daily. Platelet aggregation was reduced by amlodipine in 15.9% for ADP (10 microM); 17.4% for collagen (2 microg/ml) and 19.9% for adrenaline (2 microM) (p < 0.025). Meanwhile enalapril slightly increased platelet aggregation by 6.7%, 1.3% and 5.6% for the three agents, respectively (p > 0.05, ns). Malondialdehyde was reduced by amlodipine in 45.33% (p < 0.05) for MDA-basal; 3.76% (p > 0.05) for MDA-activated; and the ratio MDA-basal:MDA-activated in 36.79% (p < 0.005). Meanwhile enalapril increased MDA-basal in 2.89%; MDA-activated in 3.58% and reduced the ratio MDA-basal:MDA-activated, in 10.34% (p > 0.05). CONCLUSION: Both agents, enalapril and amlodipine, reduced blood pressure, but only amlodipine reduced platelet aggregation and platelet production of malondialdehyde, indicating its action on the arachidonic acid metabolic pathway.

[Platelet aggregation in arterial hypertension]. / Agregación plaquetaria en hipertensión arterial.

Hypertension is a major risk factor for stroke/myocardial infarction as expression of the atherogenic process. Platelets play a fundamental role in all these disease processes. In physiological conditions there is an equilibrium between pro aggregating and anti aggregating factors. In pathological situations this equilibrium is broken and pro aggregating factors are predominant . Patients with hypertension have an state of hyper-aggregation and dysequilibrium in the production of eicosanoids. Some antihypertensive drugs tend to not only reduce blood pressure to control levels but to reduce platelet aggregation and re-establish the broken equilibrium in eicosanoid production.

A three-locus system of interspecific incompatibility underlies male inviability in hybrids between Drosophila buzzatii and D. koepferae.

In hybrids between the sibling species D. buzzatii and D. koepferae, both sexes are more or less equally viable in the F1. However, backcross males to D. buzzatii are frequently inviable, apparently because of interspecific genetic incompatibilities that are cryptic in the F1. We have performed a genetic dissection of the effects of the X chromosome from D. koepferae. We found only two cytological regions, termed hmi-1 and hmi-2, altogether representing 9% of the whole chromosome, which when introgressed into D. buzzatii cause inviability of hybrid males. Observation of the pattern of asynapsis of polytene chromosomes (incomplete pairing, marking introgressed material) in females and segregation analyses were the technique used to infer the X chromosome regions responsible for this hybrid male inviability. The comparison of these results with those previously obtained with the same technique for hybrid male sterility in this same species pair indicate that in the X chromosome of D. koepferae there are at least seven times more regions that produce hybrid male sterility than hybrid male inviability. We have also found that the inviability brought about by the introgression of hmi-1 is suppressed by the cointrogression of two autosomal sections from D. koepferae. Apparently, these three regions conform to a system of species-specific complementary factors involved in an X-autosome interaction that, when disrupted in backcross hybrids by recombination with the genome of its sibling D. buzzatii, brings about hybrid male inviability.

Terazosin: ex vivo and in vitro platelet aggregation effects in patients with arterial hypertension.

Antihypertensive effect, platelet aggregation, and plasma lipid profile were studied in a group of 14 hypertensive patients with diastolic blood pressure between 96 and 116 mm Hg during placebo and terazosin phases. Terazosin, an alpha 1-adrenergic blocking agent, was given initially at the dosage of 1 mg daily. Then it was continued at a dosage of 2 mg daily and 5 mg daily respectively, each dosage for 4 weeks. Blood pressure was taken every 2 weeks. Ex vivo platelet aggregation induced by epinephrine, collagen, and adenosine diphosphate (ADP) were carried out twice during the first placebo phase, once at the end of each terazosin dosage, and once in the second placebo phase. Total cholesterol, HDL cholesterol, and triglycerides were measured at the end of first placebo and terazosin phases. Blood from eight patients was taken during the second placebo phase to carry out in vitro response of platelet aggregation induced by ADP, collagen, and epinephrine before and after incubation with terazosin (1, 2 and 5 micrograms/L or doxazosin (100, 200, and 500 micrograms/L for 5 min. Terazosin induced a statistically significant decrease in 14.2/8.0 mm Hg, 26.1/13.4 mm Hg, and 33.9/16.5 mm Hg in the supine position for 1, 2, and 5 mg/daily, respectively. No changes in heart rate were observed. Terazosin inhibited significant ex vivo platelet aggregation induced by epinephrine, collagen, and ADP in a range from 20% to 45% for different concentrations of inducers. Reductions in platelet aggregation seemed not to be dose dependent, as reductions were statistically equivalent for dosages of 1, 2, and 5 mg daily. Terazosin significantly reduced the level of total cholesterol (8.71%) and triglycerides (14.31%), and increased (although not significantly) levels of HDL cholesterol (3.91%). In vitro platelet aggregation was inhibited by doxazosin to a significant extent but not by terazosin.

Effects of amlodipine on platelet aggregation and blood pressure in patients with essential hypertension.

Ten patients (mean age, 46 years) with mild to moderate hypertension received 5 mg of amlodipine daily for 12 weeks. The amlodipine dose was increased to 10 mg daily in 4 patients whose blood pressure remained > or = 90 mmHg during the first 8 weeks. After 8 and 12 weeks of treatment, mean blood pressures in the supine, sitting, and standing positions and after exercise were reduced significantly. Heart rate did not change significantly from before to after treatment. Six hours after amlodipine administration, however, slight but significant increases in heart rate were noted at rest and after exercise. Platelet aggregation induced by adenosine diphosphate or collagen was significantly reduced 6 hours after amlodipine. One patient reported headache after the 10-mg dose of amlodipine. No other side effects were noted. It is concluded that 10 mg of amlodipine once daily is safe and effective in the treatment of mild to moderate hypertension.

Amlodipine in hypertension: its effects on platelet aggregation and dynamic exercise.

The antihypertensive efficacy and safety of once-daily amlodipine (5-10 mg) were studied in patients with essential hypertension. The study also included an assessment of the effects of single doses of amlodipine on platelet aggregation. Ten patients received amlodipine (mean daily dose of 7 mg) for 12 weeks in an open chronic study preceded by a 4-week placebo run-in period. Amlodipine significantly reduced the mean dorsal supine (-31/-20 mm Hg), sitting (-34/-23 mm Hg), standing (-34/ -23 mm Hg), and postexercise (-30/-20 mm Hg) blood pressures (BPs) at the end of 12 weeks of treatment compared with the placebo run-in period (p < 0.005), with no significant change in heart rate. At the end of a 4-week placebo washout phase following the chronic study, nine of the patients received an acute single 10-mg dose of amlodipine. Exercise testing before and 6 h after dosing showed that an acute 10 mg dose of amlodipine reduced BP without modifying the physiologic response to dynamic exercise. Amlodipine significantly reduced the degree of platelet aggregation in these patients (p < 0.005) induced by either collagen or ADP. This study demonstrated that amlodipine once daily was an effective antihypertensive agent and significantly inhibited platelet aggregation.

The effect of doxazosin on platelet aggregation in normotensive subjects and patients with hypertension: an in vitro study.

An in vitro assay was used to investigate the effects of doxazosin on the platelet aggregation induced by epinephrine, collagen, and adenosine diphosphate. Platelet-rich plasma from normotensive subjects and patients with hypertension was compared. Doxazosin produced a concentration-dependent inhibition of platelet aggregation in both groups, but significantly lower concentrations were required to inhibit platelet aggregation in plasma taken from patients with hypertension. The concentrations of doxazosin that inhibited platelet aggregation in vitro were similar to those that are used clinically to control blood pressure in patients with hypertension.

Evidence of an antiplatelet aggregation action of doxazosin in patients with hypertension: an ex vivo study.

Eighteen patients with a mean age of 54.7 years were included in the study. All patients had a diagnosis of mild or moderate essential hypertension (sitting diastolic blood pressure of 96 to 114 mm Hg). The study design was single blind and in two phases: phase I, placebo (4 weeks), and phase II, the active treatment (8 weeks) with increasing doses, if needed, of doxazosin every 2 weeks (1, 2, 4, and 8 mg/day). Results show that doxazosin has an antihypertensive effect that is dose dependent. Systolic, diastolic, and mean blood pressures were decreased significantly, and no effect on heart rate was observed. Doxazosin significantly inhibited the platelet aggregation induced by epinephrine, adenosine diphosphate, and collagen in a dose-dependent manner. In addition, treatment with doxazosin lowered total serum cholesterol and triglyceride levels, without changing other standard biochemical parameters. This indicates that doxazosin could offer a distinct therapeutic advantage in the modulation of atherogenic and thromboembolic factors associated with coronary heart disease.

The effects of the calcium antagonist amlodipine on blood pressure and platelet aggregation in hypertensive patients.

This study examined the antihypertensive efficacy of open-label amlodipine in once-daily doses of 5-10 mg for 12 weeks. Efficacy was assessed by measurement of blood pressure and heart rate in the supine, seated and standing positions and after exercise periodically during the study. Blood pressure was significantly reduced throughout the study with no change in heart rate. During a placebo-washout phase after the 12-week active treatment phase of the study, blood pressure returned to baseline values. After the 4-week placebo-washout phase some patients received a single 10-mg dose of amlodipine followed by an exercise test 6 h later, which showed that amlodipine lowered blood pressure without blunting the normal physiological response to exercise. In these patients amlodipine also significantly reduced ex vivo platelet aggregation induced by collagen or ADP.