Respiratory effects of pressor and depressor agents in conscious rats

We hypothesized that the respiratory baroreflex in conscious rats is either more transient, or has a higher pressure threshold than in other species. To characterize the effect of arterial pressure changes on respiration in conscious rats, ventilation (V) was measured by the plethysmographic technique during injections, or infusions, of pressor and depressor agents. Bolus injections of angiotensin II (Ang II) or arginine vasopressin (AVP), transiently increased mean arterial pressure (MAP; mean ± SE) 43 ± 6 and 28 ± 5 mmHg (1 mmHg = 133.3 Pa), respectively, and immediately reduced tidal volume (Vt) and, in the case of AVP, V. In contrast, by 10 min of a sustained elevation of MAP (40 ± 3 mmHg) with infusion of Ang II, Vt, f, and V were not different from control levels. Bolus injection of sodium nitroprusside (SNP) to lower MAP (-28 ± 3 mmHg) immediately increased breathing frequency (f) and V, whereas sustained infusion of SNP to lower MAP (-21 ± 3 mmHg) did not change f or V at 10 and 20 min. In conscious rats, both injection and infusion of the pressor agent PE (+40 to 50 mmHg) stimulated f and V; this contrasted with anesthetized rats where PE inhibited f and V, as reported by others. In conscious rats, respiratory responses associated with baroreflexes adapt rapidly and, in the case of PE, can be overridden by some other mechanism.Key words: angiotensin II, arginine vasopressin, baroreceptor reflex, phenylephrine, sodium nitroprusside.

Chronic insulin treatment in rats: Evidence against a role for insulin as a pressor agent

1. The present study was undertaken to test whether insulin acts as a pressor agent and causes hypertension in rats. 2. Insulin at doses of 10 or 100 units day−1 kg−1 was administered daily by subcutaneous injection to normal rats for 6 weeks. As it has been suggested that sodium retention plays a major role in the putative hypertensive activity of this hormone, insulin was also administered to saline- (1% NaCl) drinking rats according to the same protocol. Water- and saline-drinking rats served as controls. 3. After 6 weeks of insulin treatment, the mean arterial blood pressure did not increase in any of the insulin-treated or the insulin-salt-treated groups. However, in both insulin-salt-treated groups, absolute and relative ventricular and renal hypertrophy with increased ventricular water content as well as increased urine output with reduced osmolality were observed. 4. All insulin-treated groups showed increased plasma levels of glucose, insulin and antidiuretic hormone when compared with their respective controls. 5. These results demonstrate that chronic insulin treatment did not increase blood pressure in rats, even when drinking water was supplemented with NaCl, and suggest that a polyuria-polydipsia syndrome was present in both insulin-salt-treated groups. Moreover, increased plasma levels of antidiuretic hormone were observed in all insulin-treated groups.

Mephentermine Dependence with Psychosis

Dependence on mephentermine, a widely used sympathomimetic pressor agent, is so far unreported, although misuse of inhalers is recognised. A case of mephentermine dependence associated with chronic psychosis is reported here. Psychosis initially surfaced with chronic dexamphetamine abuse, but was sustained for 3 years by mephentermine. After a period of remission lasting for 4 years, the patient again developed psychosis on restarting abuse of mephentermine, which lasted for 5 years.

Effect of a calcium channel blocker on posttraumatic spinal cord blood flow

✓ The normal rat spinal cord blood flow (SCBF) has been shown to increase after administration of nimodipine, a calcium channel blocker. The present study investigates the capability of nimodipine to improve SCBF, as measured by the hydrogen clearance technique, after a 53.0-gm clip compression injury to the T-1 segment of the rat spinal cord. The profound drop in mean systemic arterial blood pressure (MSAP) after cervical cord injury precluded any improvement in posttraumatic SCBF by nimodipine alone. Hence, in a randomized controlled study with five rats per group, pressor agents (whole blood, angiotensin, or adrenaline) were infused to maintain MSAP between 100 and 120 mm Hg after injury. Control animals received only a saline infusion. Nimodipine at the optimal dose found in normal animals (1.5 µg/kg/min) was added to the pressor agents. The MSAP and other physiological parameters were measured in rats receiving the pressor agents only and in those receiving pressor agents combined with nimodipine. In rats receiving whole blood, angiotensin, or adrenaline the posttraumatic MSAP improved to between 100 and 120 mm Hg, but there was no improvement in SCBF compared to the saline group. The addition of nimodipine decreased MSAP and SCBF in all groups except those animals also receiving adrenaline, where the MSAP was maintained at 109 ± 5 mm Hg. In these animals a significant increase in posttraumatic SCBF from 16.5 ± 2.1 to 20.2 ± 2.3 ml/100 gm/min (mean ± standard error of the mean) occurred at the site of injury with the addition of nimodipine. The maintenance of an adequate MSAP by a pressor agent was crucial for nimodipine to improve posttraumatic SCBF by its ability to dilate the spinal vascular bed. Adrenalin was the only pressor agent that could fulfill the above criteria, although other pressor agents need to be investigated. Experiments are underway with the combination of adrenaline and nimodipine to further verify these encouraging results demonstrating an improvement in posttraumatic ischemia of the spinal cord.

Vasopressin withdrawal produces hypotension in the spontaneously hypertensive rat

In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous infusions of either arginine vasopressin (AVP, 8 mU X kg-1 X min-1) or phenylephrine (PE, 20 nmol X kg-1 X min-1) resulted in similar rises in arterial pressure. Heart rate fell greatly in the WKY but not in the SHR. Withdrawal of the PE infusion resulted in moderate decreases in blood pressure and increases in heart rate; these responses were similar in SHR and WKY. At 5 h after PE withdrawal, blood pressure and heart rate returned to basal values. In contrast, withdrawal of the AVP infusion was associated with greater falls in blood pressure and rises in heart rate. Blood pressure and heart rate in both the SHR and the WKY at 5 h after AVP were significantly different from their respective basal values. The effects of AVP withdrawal on either blood pressure or heart rate were significantly greater in the SHR than in the WKY. At 5 h after the withdrawal of AVP, blood pressure in the SHR was reduced to normotensive levels. These results suggest that the withdrawal effect was specific to AVP, was more marked in the SHR, and might not result from only the rise in blood pressure seen during the intravenous infusion of the pressor agent.