Effects of antihypertensive agents on arterial baroreceptor reflexes in conscious rats.

Abstract

The effects of antihypertensive treatment with four currently used agents (trichlormethiazide, atenolol, nicardipine, and enalapril) on the arterial baroreceptor reflex control of renal sympathetic nerve activity and heart rate were investigated in 45 conscious spontaneously hypertensive rats and 37 age-matched Wistar-Kyoto rats. Antihypertensive agents were administered for 2 weeks beginning at 8 weeks of age to treat and prevent the development of hypertension. Blood pressure was reduced to a similar level (-13±3 mm Hg,p<0.05) by each antihypertensive agent Blood pressure, heart rate, and renal sympathetic nerve activity were recorded in the conscious state during phenylephrine and nitroglycerin ramp infusion. The gain in the baroreceptor reflex was determined from the maximum slope of logistic function curves. Untreated spontaneously hypertensive rats exhibited decreased sensitivity of reflex control of renal sympathetic nerve activity and heart rate (-1.78±0.07% of control/mm Hg and -2.16±0.05 beats per minute/mm Hg, respectively) compared with untreated Wistar-Kyoto rats (-3.62±0.18% of control/ mm Hg, p<0.0l, and -3.46±0.11 beats per minute/mm Hg, p<0.05, respectively). The gains in baroreceptor reflex control of renal sympathetic nerve activity and heart rate were greater in trichlormethiazide-(-2.99±0.15%/mm Hg and -3.05±0.13 beats per minute/mm Hg, respectively), atenolol-(-3.22±0.22%/ mm Hg and -3.31 ±0.08 beats per minute/mm Hg, respectively), nicardipine-(-3.48±0.23%/mm Hg and -3.17±0.06 beats per minute/mm Hg, respectively), and enalapril-(-3.11±0.08%/mm Hg and -3-54±0.17 beats per minute/mm Hg, respectively) treated spontaneously hypertensive rats (allp<0.05) than in untreated spontaneously hypertensive rats. The antihypertensive agents affected neither blood pressure nor the baroreceptor reflex function curves in Wistar-Kyoto rats. These results indicate that attenuation of the development of hypertension by the antihypertensive agents is responsible for the restoration of impaired baroreceptor reflex control of renal sympathetic nerve activity and heart rate in conscious early hypertensive spontaneously hypertensive rats, although different antihypertensive mechanisms may mediate the blood pressure reduction. of end-organ damage are the major goals of antihypertensive therapy. Recent advances in clinical pharmacology have provided us with a huge armamentarium of antihypertensive agents. Excessive reduction of blood pressure may decrease the regional organ blood flow, leading to serious complications such as myocardial ischemia, renal dysfunction, cerebral ischemia, and at times even death. Evidence has been provided that an arterial baroreceptor reflex mechanism modifies regional blood flow 1 -2 and that the effectiveness of the baroreceptor reflex mechanism would be very limited if the resetting process was not reversible. 3Restoration of baroreceptor reflex function (i.e., normalization of reflex sensitivity and reversibility of

Impaired cardiovascular reflexes precede deoxycorticosterone acetate-salt hypertension.

“…38 Furthermore, a variety of antihypertensive agents were able to restore baroreceptor reflex control of HR and RSNA to normal as long as blood pressure was effectively lowered. 39 In prehypertensive rabbits with renovascular hypertension, the baroreceptor reflex control of HR and RSNA proved to be more sensitive compared with that in control animals. 6 These heterogeneous data do not permit general conclusions.…”

Effects of Early Treatment of Spontaneously Hypertensive Rats with an Angiotensin Converting Enzyme Inhibitor on Blood Pressure, Baroreflex Function and Cardiac Hypertrophy.

“…Because it has been shown that SHR have an impaired baroreflex control of heart rate compared with WKY (24,25), the increment in baroreflex control of heart rate may contribute to the depressor effect of captopril in SHR. In addition, oral administration of ACE inhibitors has been have shown to inhibit brain ACE activity (6,26,27). Our previous study has further shown that early treatment with captopril inhibited the pressor and drinking responses to central administration of All as well as AI suggesting that captopril produced a decrease in the number of central All receptors (20) .…”

Contribution of baroreflex sensitivity and vascular reactivity to variable haemodynamic responses to cocaine in conscious rats

“…[39][40][41] Administration of angiotensin-converting enzyme inhibitors has been shown to increase BRS independently of pressure alterations, suggesting a CNS effect. 41,42 Others have suggested that systemic AngII inhibits baroreflex function by local vasoconstriction near nerve endings in the aortic arch of rats and rabbits. 43 Baroreflex function is depressed in response to AngII injected into area postrema or nucleus tractus solitarius.…”