Vascular remodelling is well demonstrated in both human and experimental hypertension. Whether it develops in response to high blood pressure or as a marker of hypertension independently of any pressure level, it contributes in resistance arteries to maintaining an elevated blood pressure. Only recently, with the development of sensitive and reproducible methods, has remodelling of conduit arteries been assessed. A high resolution B-mode ultrasound technique can be used to measure arterial wall thickness and luminal dimension during the cardiac cycle. Changes in geometry and structure of conduit vessels have been observed in hypertensive patients or during experimental studies in animal models of hypertension. These changes may influence the buffering capacity of the conduit vessels, resulting in alteration of the dynamic component of the vascular impedance. Reduction of the systemic compliance may increase afterload and with time depress cardiac function. Ultrasonography apparatus is designed to measure local elastic properties and structural alterations and should be considered as such. Indeed, extrapolation of data acquired at a given arterial site to other parts of the vascular bed is hazardous. There exist other indirect methods based on pulse wave contour analysis and pulse wave velocity that can estimate global arterial compliance. Unfortunately, these methods have other limitations that restrict their use. Because conduit vessels represent one of the most important targets for pressure-induced lesions, namely atherosclerosis, they may be viewed as a surrogate endpoint in hypertension. Do we have evidence that vascular remodelling associated with hypertension predisposes to accelerated atherosclerosis? The purpose of this paper is to discuss the evidence that may support such a concept.
A synthetic atrial natriuretic peptide (ANF) has been administered to 7 patients with chronic renal failure to evaluate the role of ANF in the regulation of blood volume. ANF (2 micrograms/min) was infused for 60 minutes before hemodialysis and blood pressure, heart rate, plasma proteins and hematocrit were measured at regular intervals. Although a slight decrease in blood pressure occurred during ANF infusion, no significant changes in hematocrit and plasma proteins were observed. These results suggest that administration of exogenous ANF does not modify the volume distribution in patients with chronic renal failure. ANF's lack of effect is perhaps due to the chronic hypervolemia and the high plasma levels of endogenous ANF commonly found in these patients.
The traditional basis for assessing the effect of antihypertensive therapy is the blood pressure reading taken by a physician. However, several recent trials have been designed to evaluate the blood pressure lowering effect of various therapeutic agents during the patients' normal daytime activities, using a portable, semi-automatic blood pressure recorder. The results have shown that in a given patient, blood pressure measured at the physician's office often differs greatly from that prevailing during the rest of the day. This is true both in treated and untreated hypertensive patients. The difference between office and ambulatory recorded pressures cannot be predicted from blood pressure levels measured by the physician. Therefore, a prospective study was carried out in patients with diastolic blood pressures that were uncontrolled at the physician's office despite antihypertensive therapy. The purpose was to evaluate the response of recorded ambulatory blood pressure to treatment adjustments aimed at reducing office blood pressure below a pre-set target level. Only patients with high ambulatory blood pressures at the outset appeared to benefit from further changes in therapy. Thus, ambulatory blood pressure monitoring can be used to identify those patients who remain hypertensive only when facing the physician, despite antihypertensive therapy. Ambulatory monitoring could thus help to evaluate the efficacy of antihypertensive therapy and allow individual treatment.
The three angiotensin converting enzyme (ACE) inhibitors cilazapril, perindopril and CGS 14824A were administered for 8 days to, respectively, 6, 5 and 5 normotensive healthy volunteers maintained on an unrestricted salt intake. Before starting treatment, as well as on the last day of therapy, an ambulatory blood pressure profile was obtained with a semi-automatic blood pressure recorder (Remler M2000). An additional blood pressure recording was performed 1 month after the end of the 8-day course of treatment with cilazapril and CGS 14824A. Eight day ACE inhibition with any of the 3 drugs did not result in a consistent decrease of ambulatory blood pressure recordings. This suggests that in normotensive subjects on a free salt intake the renin-angiotensin system may not be a key determinant of blood pressure.
Basic examination of Mr S., 45 years of age, short in stature and overweight (1.60 m, 76 kg), was carried out because of the mild hypertension (mean AP 125 mm Hg) from which he had suffered for 20 years. The results were as follows: (1) variable hyperkalemia: plasma potassium values were 5.3 to 6.9 mmol/l; (2) normal renal function: serum creatinine 91.5 mumol/l, clearance of inulin 136.6 ml/mn; (3) proximal tubular acidosis: plasma bicarbonate and chloride values were 18.4 and 109 mmol/l, respectively; urinary pH was 7.1 with negative H+ ions urinary excretion (-33 mumol/mn); when plasma bicarbonate level was raised to 26 mmol/l by acute loading, fractional excretion of bicarbonate increased to 19,5 p. 100 while plasma potassium value decreased to 4.2 mmol/l; (4) low PRA (0.29 ng/ml/h) and normal plasma aldosterone concentration (63 pg/ml) with a normal intake of sodium and in a recumbent position. Plasma atrial natriuretic factor (ANF) level was normal: 14 fmol/ml. Intravenous infusion of ANF for 2 h (1 microgram/mn) induced the expected increases in urinary flow rate, and sodium and potassium excretions (+226, +307 and +171 p. 100, respectively). Intravenous infusion of isotonic saline (2 l in 2 h) and oral administration of fludrocortisone acetate for 4 weeks (400 micrograms per day) resulted in a normal decrease in PRA and plasma aldosterone concentration, a normal rise in plasma ANF level (22 and 42 fmol/ml) while slightly increasing AP without improving bicarbonaturia and acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
