A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

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.