Whereas it is well established that the nervous system plays a permissive role in the development of almost all experimental hypertensions, attempts to create neurogenic hypertension with repeated neurogenic pressor episodes have largely failed due to the absence of a proper stimulus. Methods to elicit pressor responses are either invasive (therefore of limited duration) or induce weak and short-lasting blood pressure elevation. We developed a new noninvasive method to elicit repeated, prolonged and potent neurogenic blood pressure elevation. In this proposal we will use this method (hindlimb compression) to: 1) Study whether repeated pressor episodes lead to cardiovascular damage and possibly sustained hypertension. 2) Study factors which accentuate and ameliorate the blood pressure response and cardiovascular damage. 3) Study secondary adaptive renal, autonomic and structural adjustments that occur in the course of prolonged pressor episodes. 4) To further investigate the mechanism of this prolonged pressor response. We anticipate that these studies will shed new light on the role of the nervous system in hypertension. Our hypotheses are: 1) that the nervous system is capable of affecting long-term blood pressure elevation and is able to override homeostatic-blood pressure lowering mechanism; 2) that repeated pressor and sympathetic overactivity periods will favor cardiovascular hypertrophy; 3) that high sodium intake will accentuate cardiovascular hypertrophy; and 4) that, independent of pressure elevations, high sympathetic activity and elevated angiotensin during hindlimb compression will favor cardiovascular hypertrophy.
| Julius, S; Li, Y; Brant, D et al. (1991) Quinapril, an angiotensin converting enzyme inhibitor, prevents cardiac hypertrophy during episodic hypertension. Hypertension 17:1161-6 |
| Buda, A J; Li, Y; Brant, D et al. (1991) Changes in left ventricular diastolic filling during the development of left ventricular hypertrophy: observations using Doppler echocardiography in a unique canine model. Am Heart J 121:1759-67 |
| Julius, S; Li, Y; Brant, D et al. (1989) Neurogenic pressor episodes fail to cause hypertension, but do induce cardiac hypertrophy. Hypertension 13:422-9 |
| Julius, S (1988) The blood pressure seeking properties of the central nervous system. J Hypertens 6:177-85 |
