Hypertension
-
Randomized Controlled Trial Clinical Trial
Nitric oxide and cardiac autonomic control in humans.
Cardiac autonomic control is of prognostic significance in cardiac disease, yet the control mechanisms of this system remain poorly defined. Animal data suggest that nitric oxide (NO) modulates cardiac autonomic control. We investigated the influence of NO on the baroreflex control of heart rate in healthy human subjects. ⋯ Relative preservation of these indexes was observed during unloading of the baroreflex with sodium nitroprusside compared with a matched fall in blood pressure produced by a control vasodilator, hydralazine (9 to 18 mg/h): DeltaRMSSD=-8+/-8 versus -24+/-15 ms (P<0.001); DeltapNN50=-6+/-11% versus -15+/-19% (P<0.01); DeltaHF normalized power=-7+/-13 versus -13+/-11 normalized units (P<0.05), respectively. The change in cross-spectral alpha-index calculated as the square root of the ratio of RR interval power to systolic spectral power in the HF band (although not alpha-index calculated in the same way for the low-frequency bands or baroreflex sensitivity assessed by the phenylephrine bolus method) was attenuated with L-NMMA compared with phenylephrine (Delta=4+/-8 versus 14+/-15 ms/mm Hg, respectively; P<0.02) and with sodium nitroprusside compared with hydralazine (Delta=-7+/-6 and -9+/-7 ms/mm Hg, respectively; P<0.05). In conclusion, these data demonstrate that NO augments cardiac vagal control in humans.
-
Randomized Controlled Trial Clinical Trial
Bradykinin B(2) receptor antagonism attenuates blood pressure response to acute angiotensin-converting enzyme inhibition in normal men.
The physiological effects of angiotensin-converting enzyme (ACE) inhibition may be in part mediated by bradykinin. We investigated the effect of coadministration of the specific bradykinin B(2) receptor antagonist icatibant on hemodynamic and neurohormonal responses to acute intravenous ACE inhibition in normal men on a normal sodium diet. We performed a 4-phase, double-blind, double-dummy, placebo-controlled study in 12 male volunteers. ⋯ Our study indicates that the bradykinin B(2) receptor antagonist icatibant attenuates the short-term blood pressure-lowering effect of acute ACE inhibition in normal men on a normal sodium diet. Bradykinin B(2) receptor antagonism alone increases resting blood pressure. Bradykinin may be involved in the control of blood pressure in the resting state in humans.
-
Increasing renal arterial pressure activates at least 3 antihypertensive mechanisms: reduced renin release, pressure natriuresis, and release of a putative renal medullary depressor hormone. To examine the role of renal medullary perfusion in these mechanisms, we tested the effects of the infusion of norepinephrine, either infusion into the renal medullary interstitium or intravenous infusion, on responses to increased renal arterial pressure in pentobarbital-anesthetized rabbits. We used an extracorporeal circuit, which allows renal arterial pressure to be set to any level above or below systemic arterial pressure. ⋯ Medullary interstitial but not intravenous norepinephrine attenuated the increased diuresis and natriuresis and the depressor response to increased renal arterial pressure. This suggests that norepinephrine can act within the renal medulla to inhibit these renal antihypertensive mechanisms, perhaps by reducing medullary perfusion. These observations support the concept that medullary perfusion plays a critical role in the long-term control of arterial pressure by its influence on pressure diuresis/natriuresis mechanisms and also by affecting the release of the putative renal medullary depressor hormone.
-
Obesity may limit sensitivity of ECG voltage criteria for left ventricular hypertrophy (LVH) because of the attenuating effects of increased body mass on precordial voltages. However, obesity is associated with an increased prevalence of anatomic LVH, making more accurate ECG criteria in obese patients a clinical priority. ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria was used to select patients for the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study. ⋯ After adjustment for age, gender, race, myocardial infarction, and diastolic and pulse pressure with the use of logistic regression analysis, increased body mass remained highly predictive of the presence of ECG LVH. Compared with normal-weight patients, obese patients had a >2-fold higher risk of ECG LVH by the Cornell product but a 4-fold lower risk of ECG LVH by Sokolow-Lyon voltage; overweight status was associated with intermediate risks, with a 151% greater likelihood of ECG LVH by the Cornell product but only 44% of the risk of LVH by Sokolow-Lyon voltage criteria compared with normal-weight individuals. Thus, Sokolow-Lyon voltage criteria underestimate the prevalence of anatomic LVH in the presence of obesity, whereas Cornell product criteria for ECG LVH appear to provide a more accurate measure of LVH in obese and overweight patients.
-
Clinical Trial Controlled Clinical Trial
Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients.
We assessed the clinical and pharmacological profile of the orally active V(1) vascular vasopressin (AVP) receptor nonpeptide antagonist SR49059 (SR) during the osmotic stimulation of AVP release in hypertensive patients. In a double-blind crossover-versus-placebo study, 24 untreated stage I or II essential hypertensive patients (12 whites and 12 blacks) received a single 300 mg oral dose of SR 2 hours before the stimulation of AVP secretion with a 5% hypertonic saline infusion. Hemodynamic, humoral, and hormonal parameters were monitored for up to 28 hours after drug administration. ⋯ SR effects were similar in the 2 ethnic groups as well as in salt-sensitive versus salt-resistant patients. In a situation of AVP osmotic release and volume expansion in hypertensive patients, a single oral dose of the V(1) vascular AVP receptor nonpeptide antagonist SR49059, which is able to block AVP-induced platelet aggregation, exerts a transient vasodilation effect that is not associated with a sustained blood pressure reduction. SR49059 is a pure V(1) vascular receptor antagonist that is devoid of V(2) renal receptor actions.