The antihypertensive effect of calcitonin gene-related peptide in rats with norepinephrine- and angiotensin II-induced hypertension.

To investigate the role of calcitonin gene-related peptide (CGRP) in blood pressure regulation, we used rats with hypertension, induced by the chronic infusion of norepinephrine or angiotensin II, and examined changes in the systemic hemodynamics using the radioactive microspheres method. CGRP (0.05 micrograms/kg per min) administered simultaneously with norepinephrine (1.8 mg/kg per day) significantly reduced the systolic blood pressure of conscious rats compared with norepinephrine infusion alone. Similarly CGRP given with angiotensin II (0.9 mg/kg per day) significantly reduced the systolic blood pressure compared with angiotensin II alone. The antihypertensive effect of CGRP was sustained for 6 days. CGRP infusion decreased the total peripheral resistance but caused no change in cardiac output compared with rats given only pressor substances. Thus, a subdepressor dose of CGRP can modulate the vasopressor effects of norepinephrine and angiotensin II. CGRP may be involved in the regulation of blood pressure via an effect on peripheral vascular resistance.

Effects of parathyroid hormone-related protein on systemic and regional hemodynamics in conscious rats. A comparison with human parathyroid hormone.

PTHrp was discovered as a humoral hypercalcemic factor of malignancy and has been shown to bind the same receptor as PTH in rat bone cells, canine renal membranes, and rabbit renal microvessels. We investigated the global effect of human PTH(hPTH) and PTHrp on systemic and regional hemodynamics in conscious rats. The hypotensive response to PTHrp was more potent than that to hPTH. Although hPTH (15 micrograms/kg/min, i.v.) caused a significant increase in cardiac output, whereas PTHrp (5 micrograms/kg/min, i.v.) caused no change in cardiac output despite a similar hypotensive effect to hPTH, the effects of PTHrp and hPTHrp on regional hemodynamics were quite similar, and both peptides had a prominent vasodilatory effect on the coronary and hepatic arteries. Therefore, PTHrp appears to have an important role in blood pressure and regional hemodynamics as does hPTH.

A case of renovascular hypertension with the nephrotic syndrome.

Nephrotic range proteinuria occurred in a 42-year-old woman with renal arterial occlusion and hyperreninemia. The administration of captopril, an angiotensin converting enzyme inhibitor, led to an amelioration of the proteinuria and the decrease of blood pressure, without surgical treatment. From the present observation, it is highly probably that the increased activity of the renin-angiotensin system plays an important role in massive proteinuria. Conservative treatment for renovascular hypertension with nephrotic syndrome was effective in this patient.

Prostacyclin production reduced in diabetics with vascular complications.

Concentrations of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of prostacyclin, were measured by radioimmunoassay before and after 3 min of induced ischemia in 45 diabetics and 23 controls matched for age. In the 45 diabetics, 15 had no vascular complications (group I), 10 had a macroangiopathy (group II), 10 had a microangiopathy (group III) and 10 had both macroangiopathy and microangiopathy (group IV). Plasma levels of 6-keto-PGF1 alpha before forearm ischemia were significantly lower in group IV diabetics than in non-diabetic controls (188 +/- 17 pg/ml and 245 +/- 14 pg/ml, respectively). After 3 min of ischemia, plasma 6-keto-PGF1 alpha concentrations were increased in control subjects by 34% and by 21% in group I diabetics. In group III diabetics as well as diabetics with atherosclerotic vascular lesions (groups II and IV), no significant change was observed after 3 min of ischemia. These results suggest that impaired vessel wall prostacyclin production may to some extent be responsible for the development of diabetic retinopathy and nephropathy as well as atherosclerotic vascular complications.

Left ventricular function in patients with diabetes mellitus.

The left ventricular function was assessed in 70 diabetics under 60 years of age without clinically evident heart disease using established non-invasive methods, these include systolic time interval method and echocardiography. The ratio of pre-ejection period to left ventricular ejection time (PEP/ET) was remarkably elevated in diabetics with severe microangiopathy (0.431 +/- 0.037). Even in diabetics without microangiopathy PEP/ET ratio was significantly higher (0.374 +/- 0.037) compared with that in controls (0.331 +/- 0.023, P less than 0.01). Most of diabetics with a PEP/ET value of higher than 0.40 were not under proper care with regard to diabetic control. A tendency toward normalization of PEP/ET values was often observed with the improvement in diabetic control during six to twelve months among the inadequately controlled diabetics. Isovolumic relaxation time in diabetics was longer than in controls (80 +/- 14 msec, 59 +/- 11 msec, P less than 0.005). Our results suggest that abnormalities of left ventricular function in diabetics may be related to not only severity of microangiopathy but also the state of diabetic control. The maintenance of adequate control of diabetes seems to play an important role in the prevention of congestive heart failure in patients with diabetes mellitus.

A study of long-term observations in borderline hypertension.

To identify the risk factors of borderline hypertension in the development of established hypertension, the relationship between the changes in blood pressure over 10 years and the clinical features in the initial year was investigated in a Japanese urban population. The occurrence of cardiovascular complications in cases with borderline hypertension were also studied. The prevalence of borderline hypertension in the initial year was 18.2%. On the basis of the blood pressure changes over 10 years, these subjects could be classified into the following 5 groups: (I) those with developing established hypertension, 19.0%; (II) those with fluctuating between hypertension and borderline hypertension, 27.4%; (III) those with remaining with borderline hypertension, 19.6%; (IV) those with fluctuating between borderline hypertension and normotension, 22.9%; (V) those with improving to normotension, 11.2%. The later development of established hypertension was found in only 2.4% of normotensives in the initial year. Obesity and glucose intolerance were more frequently observed in group I (38.2% and 29.4%, respectively) than in the other groups. Diastolic blood pressures in the initial year were significantly higher in groups I and II than in III, IV and V. As for the occurrence of cardiovascular complications during the observation period, electrocardiographic abnormalities and hypertensive and/or arteriosclerotic retinopathy were not infrequently observed even in borderline hypertensives. Therefore, in subjects with borderline hypertension, continuous medical management, including correction of obesity as well as glucose intolerance, is necessary to prevent the development of established hypertension and subsequent cardiovascular complications.