Platelets in nonresponders to epinephrine stimulation showed reduced response to ADP.

It has been reported that platelets from some healthy donors did not respond to epinephrine (Epi). To identify the cause for the lack of response, we examined the alpha(2) adrenoceptor in the platelets and their signal transduction pathways. No differences in the genomic (-2076 to 1526 bp) and coding region of alpha(2A) adrenoceptor complementary DNA (cDNA) were found between the responders (R) and nonresponders (NR). No expression of alpha(2B) or alpha(2C) adrenoceptor was detected in platelets. When UK14,304 was used to induce platelet aggregation, similar effect to Epi was observed between R and NR, and any involvement of the alpha(1) and beta adrenoceptor was ruled out. Radioligand binding assay showed similar number of alpha(2) binding sites between the two groups (139+/-25/platelet vs. 145+/-37/platelets). However, platelets from NR showed a weaker response to adenosine diphosphate (ADP, 52.3+/-17.8% vs. 80.5+/-8.7% from R, P<.01). In the presence of P2Y(1) antagonist adenosine 3',5'-diphosphosulfate (A3P5PS), ADP failed to induce platelet aggregation in NR (7.8+/-4.7% vs. 64.7+/-11.2% in R, P<.01). Addition of SQ22,536 to inhibit adenylyl cyclase did not convert NR to R. These observations demonstrate that there is an impaired platelet responsiveness to ADP as well as to Epi in NR, due to a difference in downstream of the signal transduction pathway but independent of adenylyl cyclase inhibition.

[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan].

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.