Abstract— Subcellular distribution of substance P as measured by radioimmunoassay was studied in fractions and subfractions from bovine hypothalamus and substantia nigra. Most of the substance P was found in the crude mitochondrial fraction. Subfractionation of the crude mitochondrial fraction by density gradient centrifugation showed most of substance P was present in nerve ending particles. Subcellular particle integrity was assessed using enzyme markers.

Twenty patients with uncontrolled hypertension were treated with pinacidil for a mean period of 43 weeks (range 10-63 weeks). All patients achieved and maintained significant reductions in blood pressure. The supine blood pressure at baseline was 184/116 mmHg; after one week it was 161/95 mmHg and at 43 weeks it was 138/79 mmHg. The mean dose of pinacidil was 30 mg/day. There was no significant difference between the two groups with respect to the dose of pinacidil or the blood pressure response. Pulse rate and weight remained stable for the group as a whole. Five patients were not taking beta-blockers. The mean baseline pulse rate for this group was 78 beats/min and when maintained on pinacidil it was 82 beat/min (NS). Six patients were not taking diuretics. The mean baseline weight for this group was 78.5 kg and while maintained on pinacidil it was 79.2 kg (NS). There was no occurrence of oedema, hirsutism or first dose phenomenon. The mean glomerular filtration rate and renal plasma flow for the renal plasma flow for the renal group was 35.4 ml/min and 192.3 ml/min before pinacidil and after six months they were 32.7 ml/min and 183.2 ml/min (NS) respectively. Six patients experienced minor side-effects. We conclude that pinacidil is a potent, well tolerated antihypertensive agent which merits further study.

In an open study, thirteen chronic dialysis patients with nonvolume dependent uncontrolled hypertension were treated with pinacidil for a mean period of 43 weeks. Seven patients were taking concomitant antihypertensive therapy. Twelve patients achieved long-term blood pressure control on a mean dose of 33 mg/day. The baseline supine blood pressure was 184/116 mmHg. After 1 week it had fallen to 161/95 mmHg and blood pressure control was maintained over the study period. Patient weight remained stable. The baseline reading was 61.6 kg and at the end of the study it was 59.7 kg. Pulse rate did not change significantly. For the eight patients not taking beta-blockers the mean change in pulse rate was 7.6 beats/min supine and 6.3 beats/min erect (NS). Pretrial urea and creatinine were 27.6 mmol/l and 1027 mumol/l and after 25 weeks they were 29.6 mmol/l and 1087 mumol/l, respectively (NS). Four patients had ECG evidence of left ventricular hypertrophy before the study and one on completion of the trial. Five patients showed correction of T-waves on their ECG's. Six patients experienced side effects, none of which warranted withdrawal of treatment. These findings suggest that pinacidil is a valuable alternative treatment for hypertensive dialysis patients.

No abstract