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Objective: To evaluate oral misoprostol use before office endometrial biopsy., Methods: Forty-two nonpregnant women aged 35-77 years were randomized to a prospective, double-blind study to receive either 400 microg oral misoprostol or placebo 3 hours before office endometrial biopsy. Misoprostol effects were assessed by 1) cervical resistance, 2) ease of performing the endometrial biopsy, 3) success rate of obtaining an endometrial biopsy, 4) pain intensity associated with the endometrial biopsy, and 5) adverse clinical side effects., Results: Patients in the misoprostol group experienced significantly (P <.01) more pain associated with the endometrial biopsy. The observed power to detect this difference in misoprostol-placebo comparison using the Wilcoxon rank sum test at 0.05 level of significance is 89%. In addition, significantly (P <.05) more patients had the adverse side effect of uterine cramping at 1.5 hours after medication ingestion in the misoprostol group. The observed power to detect this difference is 98%. There were no differences between the misoprostol and placebo groups in cervical resistance, ease of performing the biopsy, success rate for obtaining an endometrial biopsy, or adverse side effects at 3 hours post medication ingestion., Conclusion: Oral misoprostol 400 microg caused more uterine cramping and pain in nonpregnant women undergoing office endometrial biopsy when given 3 hours before biopsy attempt. No other cervical effects were noted.

Background: Angiotensin II type 1 (AT1) receptor antagonists, when given over the long term, reduce the deleterious consequences of ischemia-reperfusion injury. Whether short-term administration of AT1 or angiotensin II type 2 (AT2) receptor antagonists is cardioprotective has not been investigated., Methods and Results: The effects of short-term administration of selective AT1 and AT2 receptor antagonists on the recovery of mechanical function during reperfusion after 30 minutes of global, no-flow ischemia were studied in left atrium-perfused isolated working rat hearts. Control hearts (n = 8) showed incomplete recovery of left ventricular minute work (LV work) and cardiac efficiency during reperfusion to 51 +/- 15% and 61 +/- 19% of preischemic levels, respectively. Compared with control hearts, the selective AT2 receptor antagonist PD123,319 (0.3 mumol/L) given before ischemia (n = 7) improved the recovery of LV work and efficiency to 82 +/- 4% and 98 +/- 7% of preischemic levels, respectively (P < .01). In contrast, the selective AT1 antagonist losartan (1 mumol/L) blocked the recovery of LV work and depressed efficiency to 0 +/- 0% and 1 +/- 0% (n = 7) of preischemic levels, respectively (P < .01; n = 7). Neither antagonist altered coronary vascular conductance., Conclusions: This is the first demonstration that short-term treatment with a selective AT1 versus AT2 antagonist exerts different effects on recovery of mechanical function after ischemia-reperfusion: the AT2 antagonist was cardioprotective, whereas the AT1 antagonist was not. These data suggest that AT2 antagonists and AT1 agonists may offer novel approaches for the treatment of mechanical dysfunction after ischemia-reperfusion.

The negative inotropic responses of guinea pig isolated left atria to the P1-receptor agonists adenosine and L-N6-phenylisopropyladenosine (L-PIA), the muscarinic receptor agonist carbachol, and the potassium channel activator cromakalim were examined. The potassium channel blocker 4-aminopyridine (4-AP, 10 mM) decreased the concentration-response curve for L-N-6-phenylisopropyladenosine (L-PIA) so that the maximum reduction in atrial tension was significantly reduced from 77.8 to 61.9%. The concentration-response curve for the negative inotropic response to carbachol was displaced to the right by a substantially greater amount (521-fold), partly due to the muscarinic receptor blocking activity of 4-AP. The response to a single submaximum dose of L-PIA (520 nM) was slow in onset and monophasic, whereas adenosine induced a rapid reduction in tension followed by a gradual return toward the resting level. In the presence of 4-AP (10 mM), the peak response to L-PIA was significantly reduced from a 59.7 to 31.0% inhibition of tension. In addition, the rate of development of the response was significantly slowed. The peak inhibition of tension by adenosine (112 microM) (60.0%) was also significantly reduced to 37.4% in the presence of 4-AP (10 mM). Furthermore, there was no rapid decrease in tension but a gradual decrease to a peak effect which was no different from that in the absence of 4-AP. These results suggest that the P1-receptor agonists exert negative inotropy through a K+ channel-dependent component which is blocked by 4-AP and a slower-onset K+ channel-independent component. The potassium channel blocker, bromobenzoylmethyladamantylamine (BMA 100 microM) also shifted (11-fold) the concentration-response curve for the negative inotropic response to adenosine, and to a lesser extent that to cromakalim (2.1-fold) and carbachol. Glibenclamide (0.3, 3, and 30 microM), a selective antagonist of ATP-regulated potassium channels, was a potent antagonist of the negative inotropic responses to cromakalim. However, 30 microM failed to antagonize the responses to L-PIA, adenosine, or carbachol, indicating that they do not mediate their responses through ATP-regulated potassium channels. 4-AP (10 mM) caused a slight shift (2.3-fold) of the concentration-response curve for cromakalim, indicating weak activity against ATP-regulated potassium channels in the left atrium. This study showed that P1-receptor agonists exert negative inotropic responses in guinea pig left atria only in part through activation of potassium channels. These channels differ from the ATP-regulated potassium channels activated by cromakalim.